Full Text CA-95-011

COOPERATIVE GROUP FOR BREAST AND COLO-RECTAL CANCER CLINICAL TRIALS

NIH GUIDE, Volume 24, Number 19, May 26, 1995

RFA:  CA-95-011

P.T. 34

Keywords: 
  Clinical Trial 
  Cancer/Carcinogenesis 
  0715036 
  Digestive System 


National Cancer Institute

Letter of Intent Receipt Date:  June 23, 1995
Application Receipt Date:  August 25, 1995

PURPOSE

The Division of Cancer Treatment (DCT), National Cancer Institute (NCI)
invites applications for cooperative agreements to establish a
surgically oriented, Clinical Trials Cooperative Group (henceforth
termed the Group) that will perform multi-institutional clinical trials
in adult patients with breast and colo-rectal cancer.  The Group will
be expected to conduct a broad spectrum of innovative therapeutic
clinical trials that will advance the care of these patients.

The NCI's Clinical Trials Cooperative Groups consist of researchers at
affiliated institutions who jointly develop and conduct cancer
treatment clinical trials in multi-institutional settings.  They are a
major component of the extramural research effort of the Division of
Cancer Treatment.  Each Group is supported to continually generate new
trials compatible with its particular areas of interest and expertise,
as well as with national priorities for cancer treatment research.
Unlike most other major National Institutes of Health (NIH) cooperative
clinical trials efforts, Group structure and funding are not usually
linked to any specific clinical trial(s).  This mechanism thus has the
potential for considerable flexibility in resource allocation, and for
the rapid testing of promising new cancer therapies in large patient
populations, since the apparatus for conducting such trials is
constantly in place.  The Groups have been instrumental in the
development of new standards of cancer patient management and
sophisticated clinical investigation techniques.

Further information on the DCT Clinical Trials Cooperative Groups can
be found in the CLINICAL TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES,
available from the NCI Program Director listed under INQUIRIES.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Cooperative Group for Breast and Colo-Rectal
Cancer Clinical Trials, is related to the priority area of cancer.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by North American, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.  In
addition, health maintenance organizations (HMOs) are eligible.
Foreign organizations outside North America are not eligible to apply.
Applications that include minority individuals and women as Principal
Investigators are encouraged.  Eligible institutions may apply for one
or more of the following types of awards:

o   Headquarters/Operations Office
o   Main Members
o   Statistical and Data Management Center

Separate applications must be submitted for each type of award.  Each
Headquarters/Operations Office applicant must identify in both a cover
letter and in the body of the application a single Statistical and Data
Management Center with which it is proposing to collaborate.  Each
applicant for a Main Member award must identify in both a cover letter
and in the body of the application the Headquarters/Operations Office
with which the applicant is proposing to work.  Each applicant for a
Statistical and Data Management Center must identify both in a cover
letter and in the body of the application the Headquarters/Operations
Office with which the applicant is proposing to collaborate.

It is the responsibility of potential applicants for the three
components of the Group - Headquarters/Operations Office, Main Members
and Statistical and Data Management Center - to identify themselves to
each other and to establish affiliations.  Main Member institutions can
be members of other Cooperative Groups, but the research performed by
the Main Member in other Groups can not overlap with the workscope of
this RFA, and this should be  made clear in the application.  For this
RFA, Main Member applicants can only affiliate with one
Headquarters/Operations Office applicant.

Each applicant for a Headquarters/Operations Office Group must
demonstrate the ability to recruit and support adequate membership to
ensure the ability to mount multiple, concurrent large scale (sample
size > 1000 patients) randomized clinical trials in different
prognostic subsets in breast and colo-rectal cancer.  Each Main Member
applicant must demonstrate the capability to accrue a minimum of 30 new
patients per year.

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for this RFA will
be the cooperative agreement (U10), an assistance mechanism, in which
substantial NCI scientific and/or programmatic involvement with the
awardee is anticipated during performance of the activity.  Under the
cooperative agreement, the NCI's purpose is to support and/or stimulate
the recipient's activity by involvement in and otherwise working
jointly with the award recipient in a partner role, but it is not to
assume direction, prime responsibility, or a dominant role in the
activity.  The U10 cooperative agreements are cooperative research
programs between the Sponsoring Institute and participating principal
investigators and institutions whose research is usually conducted
through established protocols in multi-institutional settings.

Details of the responsibilities, relationships, and governance of the
study to be funded under this cooperative agreement are discussed later
in this RFA under the section Terms and Conditions of Award.

Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of the award(s) will
vary also.

The total project period for applications submitted in response to the
present RFA may not exceed five years.  The anticipated award date is
March 1, 1996.  Although this program is provided for in the financial
plans of the NCI, awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.

This RFA is a one-time solicitation.  However, if it is determined that
there is sufficient continuing program need, the NCI will invite
recipients of awards under this RFA to submit competitive continuation
cooperative agreement applications for review according to the CLINICAL
TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES, available from the NCI
Program Director listed under INQUIRIES.

FUNDS AVAILABLE

Approximately $9 Million total costs will be available in fiscal year
1996 for the first year of support for awards made under this RFA.  It
is anticipated that only one Cooperative Group will be supported by
awards via this RFA in fiscal year 1996.  The level of support will be
dependent upon the number of applications of high merit received and
the availability of funds.  Funding beyond the initial budget period
will be contingent on the continued availability of funds for this
purpose and the continued progress of the awardee and the Group as a
whole.

RESEARCH OBJECTIVES

Background

Breast cancer afflicts more than 180,000 women annually in the U.S.
while cancer of the large bowel (colon-rectum) was estimated to occur
in 75,000 men and in 74,000 women in 1994.  Jointly, these two tumor
sites represent nearly one third of all adult cancers and are estimated
to cause death in over 102,000 Americans each year.  Despite the
obvious anatomic differences, the therapeutic approach developed for
these cancers is analogous in many respects as is the need for
improvement of our standard therapies.  Early detection leads to better
outcome, but screening tools remain suboptimal.  Initial treatment is
usually surgical, although improved understanding of tumor progression
has led to the use of less radical surgical procedures.  Involvement of
lymph nodes portends systemic involvement, and thus reflects the need
for adjuvant systemic treatment.  Although effective adjuvant treatment
is available, many patients still relapse despite such treatment.  The
advent of newer, biologic markers has defined subsets of node negative
patients that have a high risk of relapse, and therefore merit
consideration for adjuvant therapy.  Advanced disease remains largely
incurable so that its treatment is presently geared towards palliation
of symptoms and enhancement of quality of life, and finally,
chemoprevention is under study for both.  As better genetic definition
of high risk becomes available for breast and colo-rectal cancer, the
need for effective preventive options is likely to increase.

The current treatments used for breast and bowel cancer vary according
to disease stage but are often characterized by a multimodality
approach.  Since early stage disease can often be cured by surgery
alone, the emphasis in this setting has centered on conservative
surgery, utilizing radiation, in some instances, to control microscopic
disease.  For more advanced tumors at higher risk of systemic spread,
chemotherapy in both diseases and hormonal maneuvers in breast cancer
have improved survival rates at 5 to 10 years by approximately 10 to 15
percent.  However, the past twenty years of trials with systemic
therapies have demonstrated that progress is usually incremental, and
large phase III trials are often needed to detect small, yet
meaningful, benefits.  These characteristics make it evident that the
cooperative efforts of specialists within institutions and partnerships
among many different centers are required if further therapeutic
advances in these tumors are to be achieved.  Practitioners of  general
surgery are often involved early in the diagnosis and detection of
these malignancies so that assuring them a key role in this Group
should enhance its ability to perform innovative treatment and
prevention trials.

Improvements in our understanding of tumor promotion, growth, and
metastases have occurred over the past decade in the fields of breast
and bowel cancer.  In order to translate this knowledge into clinical
benefit, a collaboration between laboratory scientists and clinical
researchers is required.  The NCI is therefore seeking a surgically
oriented, multidisciplinary and multi-institutional team of talented
scientists from academic and community medical centers to form a
Clinical Trials Cooperative Group that will interact with the Cancer
Therapy Evaluation Program (CTEP) staff in a concerted way to conceive,
create, and evaluate new approaches to the treatment of breast and
bowel cancers.  Furthermore, NCI is encouraging this Group to include
women scientists and members of minority groups, who are recognized
experts, in positions of both scientific and administrative leadership.

Although new treatment ideas will come from diverse arenas such as
pharmaceutical industry research and single institution trials, the NCI
wishes this Group to have among its members sufficient academic
research institutions capable of performing phase I and II trials, so
that original ideas can be brought to the Group to serve as the basis
for phase III comparisons.  Scientific approaches should be broad and
reflect the creativity and capabilities of team participants, including
surgical, medical, radiotherapeutic, laboratory, diagnostic imaging,
and statistical skills.  Team objectives and approaches will be
investigator-originated but consistent with program aims of improving
the survival and quality of life for persons with breast and bowel
cancers or those at risk for these diseases.

Other

A.  Objectives and Scope

The purpose of this RFA is to stimulate the development of innovative
phase III clinical trials for the treatment of early stage breast and
colo-rectal cancer.  Phase I, II, and even phase III trials in
metastatic disease are acceptable as long as the goal in developing
these studies is to advance the treatment of early stage disease.
Furthermore, a focus on surgical expertise is required so that
innovative surgical treatments, such as laparoscopic abdominal surgery,
guided axillary dissection and rectum sparing approaches, can be fully
explored.  Highlighting surgical participation also ensures the
inclusion in the Group of medical "gatekeepers" who are ideally
situated for participation in early detection, diagnostic, and
preventive strategies.  In addition, this surgical orientation should
facilitate the collection of adequate tumor tissue and serum specimens
for tumor banking and studies of the genetic and molecular changes
with, or predisposing to, breast or colo-rectal cancer.

Examples of potential innovative therapeutic approaches include: tumor
vaccines and monoclonal antibodies against tumor-specific antigens, and
monoclonal antibodies against tumor neovasculature; evaluation of
retinoids, vitamin D analogs and other differentiating agents; testing
of new chemotherapeutic agents such as topoisomerase I inhibitors,
taxanes, thymidylate synthase inhibitors, edatrexate, and navelbine;
development of pilot trials using intermediate endpoints for prevention
of breast and bowel cancer;  exploration of critical markers which
indicate treatment sensitivity or resistance (e.g., cerbB-2, p53, tumor
angiogenesis markers, thymidylate synthase) and detection of genetic
changes in high risk individuals (BRCA-1, BRCA-2, HNPCC/MSH2); surgical
studies of laparoscopic techniques for bowel resection vs. standard
procedures, rectal-sparing approaches, trials studying the role of
axillary dissection, surgical approaches to in situ breast cancer, and
studies of the role of menstrual timing for breast surgery.

In order to accomplish these research objectives, the scope of
activities of this Clinical Trials Cooperative Group should include:

1.  the ability of the membership to accrue large numbers of patients
with early stage breast and colo-rectal cancer;

2.  scientific leadership in these diseases including both clinical and
laboratory expertise;

3.  a statistical office with leadership that has proven experience in
designing, conducting and analyzing phase I-III clinical trials.

4.  a membership performance review program that emphasizes
productivity as measured by both high quality record-keeping and
adequate accrual;

5.  a tumor banking system that facilitates integration of correlative
studies into the overall research effort;

6.  detailed methods for assuring inclusion in these trials of adequate
numbers of women and minority patients;

7.  the capability to perform pilot trials in metastatic disease
preparatory to phase III adjuvant trials;

8.  clinical research in diagnostic, epidemiologic, cost-effectiveness,
quality of life, cancer control, and prevention trials, although not
required, can serve to enhance Group science and the applicability of
the research. Interest and expertise in these areas will enhance the
application;

9.  integration of members of the patient advocate community into
appropriate Group committees and activities;

10.  capability in dealing with regulatory responsibilities such as
Investigational New Drug (IND) issues and drug shipments and handling;
and

11.  quality assurance and quality control programs that will ensure
both a high quality of clinical research and patient safety.

B.  Organization

The Group will consist of three major operational components:  the
Headquarters/Operations Office, the Statistical and Data Management
Center, and the Participating Investigators' Institutions.  Each
component has general responsibilities in meeting the goals and
objectives outlined above or in completing tasks necessary to
accomplish those goals.  The Group will be governed by a written
constitution and bylaws, which should describe membership criteria for
inclusion and exclusion, procedures for selecting Group leadership and
other details of governance, and will be led by a chairperson who is
ultimately responsible to the membership and to the NCI for the content
and conduct of the Group's research program.  Beyond this requirement,
the structure and management of the Group is the responsibility of the
Group itself to determine.

The following sections describe the responsibilities and functions of
each of the three operational components.

1.  Headquarters/Operations Office

The Headquarters/Operations office is the direct responsibility of the
Group chairperson.  It provides executive leadership and day-to-day
administrative management of the Group.  Through this office the
chairperson implements the Group's scientific and organizational
policies.  Specific roles and responsibilities include the following:

a.  Provide general scientific oversight, assuring development of
research plans for each disease and/or modality in the Group's
repertoire and the maintenance of a clear sense of the Group's overall
research priorities.

b.  Develop and provide to the Group membership and to NCI, a
Constitution and By-Laws specifying Group structure and management,
procedures for the selection of the Group Chair and other leadership,
terms of office, criteria for membership, and other details of
governance of the Group.

c.  Provide, to the membership and to the NCI, policies and procedures
for the conduct of the Group's activities.

d.  Serve as the Group's communication and information dissemination
hub for investigators and institutions within the Group and individuals
and organizations outside of the Group.

e.  Provide overall management of the Group's resources, assuring
allocation to high priority projects and to the most productive
activities and members.

f.  Provide logistical and financial support to the Group's scientific
committees, monitor their productivity, and provide for the
election/appointment of their leadership.

g.  Provide organizational and logistical support for the Group's
meetings.

h.  Conduct periodic review of the performance and membership status of
each Main Member/Affiliate according to criteria established by the
Group; this review should examine scientific contributions, patient
accrual and follow-up, data accuracy and timeliness, protocol
compliance, audit results, and adherence to regulatory requirements.

i.  Establish a Data and Safety Monitoring Committee (DSMC) for Phase
III trials in accordance with NCI Guidelines, and provide
organizational and logistical support to the DSMC.

j.  Develop procedures for study monitoring to assure compliance with
protocol design and protection of patients from research risks.  This
medical review should be coordinated with the quality assurance and
quality control programs managed by the Statistical and Data Management
Center.

k.  Encourage and provide financial support for the integration of
community participation (patients and patient advocates)in the Group's
activities by including them in Group meetings and on appropriate
committees.

l.  Foster and monitor the inclusion of women and ethnic minorities in
the Group's clinical trials.

m.  Provide logistical and clerical support to the process of protocol
development; develop and implement standards for protocol format.

n.  Assure internal Group and CTEP review and approval of protocol
concepts, final protocol documents, informed consents and study
amendments; advise CTEP of changes in protocol status.

o.  Produce and maintain current and accurate Group records.

p.  Oversee Group compliance with regulatory requirements concerning
the use of investigational agents, the reporting of adverse events, and
the protection of human research subjects (see also t. and u. below).

q.  Provide guidance to the membership regarding clinical trials
practices, including ethical issues involved in clinical research and
conflict of interest considerations.

r.  Track the progress of the Group's research and assure that results
of Group trials are published in appropriate peer-reviewed literature
in a timely manner and in accordance with Group publication policies.

s.  Assist member institutions in the process of preparing competing
renewal applications.

t.  Verify that all membership sites have an approved Cooperative
Project Assurance (CPA), or Multiple Project Assurance (MPA) as
required on file with the Office for Protection from Research Risks
(OPRR), DHHS.  Physicians in private practice must have an approved
Non-Institutional Investigator Agreement (NIA) on file with the
Headquarters/Operations Office.

u.  Monitor and maintain appropriate records of protocols, informed
consents, assurances and annual certifications of Institutional Review
Board (IRB) review and approval (HHS Optional Form 310) for all Main
Members and Affiliates.

v.  Manage and allocate financial resources from the Developmental
Fund.  The purpose of the Developmental Fund is to provide the Group
leadership with resources to support new initiatives, special
high-priority projects, and limited funding for candidate members.

w.  Provide third party payments to relevant participating Affiliates
that do not hold cooperative agreements from the NCI.

2.  Statistical and Data Management Center

A Group's statistical and data management staff are integral
collaborators in all stages of study development, conduct, analysis and
reporting.  In addition, the Statistical and Data Management Center
funded by this RFA will have responsibility for the Group's quality
control and quality assurance programs including the development and
implementation of an on-site audit program.  The general operational
responsibilities usually assumed by this component include:

a.  Ensure study feasibility and appropriateness of study design with
respect to stated study objectives.

b.  Ensure that there are clear and consistent definitions of study
objectives, eligibility criteria, primary analysis endpoints,
evaluation criteria (such as toxicity and response definitions) and
guidelines for removal of patients from protocol therapy.

c.  Develop non-standard designs when necessary to achieve specific
study objectives.

d.  Take primary responsibility for the establishment and conduct of
quality control and on-site auditing.  The Statistical Office will
conduct the Group's on-site monitoring program and will be responsible
for adherence to the NCI/CTMB GUIDELINES FOR ON-SITE MONITORING OF
CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES
available from the NCI Program Director or from the Clinical Trials
Monitoring Branch (CTMB), CTEP upon request.  The Statistical Office
will  provide logistical and financial support for the Group's quality
control programs.

e.  Implement plans for monitoring of study data, including planned
interim analyses of studies and timely reporting to the DSMC of all
toxicities. Interim study reports should be prepared according to Group
policies in this regard.  In general, reports of accrual, eligibility,
evaluability, and toxicity should be made for each open study on at
least a semi-annual basis.

f.  Implement appropriate registration, randomization procedures, and
accrual tracking procedures.

g.  Design, develop and implement forms required to collect Group study
data.

h.  Provide for all aspects of the collection and management of Group
study data, especially quality and timeliness of data submission.

i.  Contribute to all decisions regarding the conduct of Group studies.

j.  Perform statistical analyses that use state-of-the art methodology
and provide unbiased results.

k.  Co-author articles and abstracts based on protocol results and
other Group data where appropriate; publish on methodologic issues in
cancer clinical trials.

3.  Participating Investigators/Membership Categories

Investigators participating in Group research may come from a wide
variety of academic and practice settings.  Recognizing current
realities of oncologic practice, the NCI provides various mechanisms of
financial support for motivated investigators, including the Main
Member (and its designated Affiliates) cooperative agreement (awarded
directly by the Division of Cancer Treatment, NCI), the Community
Clinical Oncology Program (CCOP) cooperative agreement (awarded
directly by the Division of Cancer Prevention and Control, NCI),
third-party payments (subcontracts or purchased service agreements) for
Affiliate member institutions which do not hold cooperative agreement
awards (awarded through the Headquarters/Operations Office) and the
other special initiative programs such as the High Priority Trials
Program and the Minority Initiative Program (awarded through the
Headquarters/Operations Office). Participating investigators may
receive additional funds through the Headquarters Office for the
conduct of administrative, scientific, laboratory or high priority
tasks which are within the workscope of the Group.

The Group shall establish policies and procedures for credentialling
participating institutions and conducting periodic review of the
performance and membership status of all membership sites.  This review
should examine scientific contributions, patient accrual, data accuracy
and timeliness, protocol compliance, procedures for lifetime tracking
and follow-up of patients, and audit results.  Reimbursement for the
costs of participating in Group research must be linked to the quality
of institutional performance.

a.   Main Members

Main Member institutions can be North American, for profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal Government.  In
addition, health maintenance organizations (HMOs) are eligible.  In
addition to patient accrual, substantial importance is placed on
scientific and administrative contributions to the Group.  The Group
shall establish its own specific criteria for membership and a formal
process for application.  In most Groups, institutions are initially
admitted for membership on a provisional basis.  Eligibility for
institutional cooperative agreement awards is limited to institutions
which have been granted full membership by the Group, and continued NCI
funding is contingent upon maintenance of satisfactory membership
status.  Investigators at Main Member institutions are expected to:

1)  Actively participate in the Group's scientific committees.

2)  Serve as Study Chairs responsible for the development and conduct
of specific Group studies.

3)  Contribute their independent laboratory and clinical research
experience to the Group.

4)  Actively participate in Group meetings.

5)  Accrue a minimum of 30 patients annually to Group protocols.

6)  Submit timely and accurate patient data to the statistical office.

7)  Author manuscripts and abstracts to disseminate the results of
Group studies.

8)  Participate in the Group's on-site audit program.

9)  Serve on Group administrative committees.

10) Periodically serve on NCI site visit teams and peer review
committees.

11) Develop community outreach programs that involve patients and
patient advocates in the Group's research in a productive and
meaningful manner.  This effort should be coordinated with the
Headquarters/Operations Office.

12) Foster and monitor accrual of women and ethnic minorities to Group
trials.

13) Assume responsibility for all Group activities conducted at his/her
own institution and at Affiliate institutions (see b. below for
Affiliate membership criteria).

b.  Affiliate Members

Two categories of Affiliate membership will be permitted:

1)  In category 1, Affiliate Members are proposed by Main Member
institutions and represent sites of scientific or clinical expertise
that are judged by the Main Member institution to contribute
significantly to the quality of that institution's programs.  Thus,
Main Members seeking to sponsor Affiliates should be able to
demonstrate reasonable geographic proximity to the Affiliate
institution and past evidence of successful clinical collaboration in
order to guarantee that the Main Member will be able to provide
adequate oversight of the Affiliate Member.  In addition, Affiliate
Members are required to accrue a minimum of 10 eligible patients
annually.  They should also demonstrate quality record-keeping and
strict adherence to all regulatory and human subjects requirements for
clinical trials.  This necessitates that all Affiliates have an
assurance which is approved by OPRR and that its IRB is willing to
assume responsibility for all the investigators associated with the
Affiliate.  If an Affiliate does not have an IRB and wishes to make an
arrangement with the IRB of another Affiliate or Main Member, such
arrangements must be approved by OPRR.  In addition, all Affiliate
investigators who are in private practice must complete a
Non-Institutional Investigator Agreement which is co-signed by the
responsible IRB and is on file at the Group Headquarters/Operations
Office.

Reimbursement of Affiliates in category 1 will be via a capitation (per
patient research-cost reimbursement) system.  Overall data quality as
well patient accrual will be utilized in determining reimbursement for
research costs.  The specific criteria for determining reimbursement
are the responsibility of the Main Member, but must be consistent with
the overall performance review guidelines for Group membership as
determined by the Headquarters/Operations Office.  However,
reimbursement of Affiliates will be capped at an amount equivalent to
the research costs for 30 patients annually. Once an Affiliate has
demonstrated the ability to accrue patients at this level, it should be
encouraged to apply for Main Member status.  On-site auditing of
Affiliates may be the responsibility of the Main Member, and/or the
Statistical Office depending on the auditing plan developed by the
Statistical and Data Management Center, and shall be in accordance with
the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR
COOPERATIVE GROUPS AND CCOP RESEARCH BASES.  Affiliates will be
responsible for directly registering all patients onto study protocols
through the Group Headquarters/Operations Office, thus assuring that
accrual can be accurately tracked by Affiliate site.  Finally, all
nominations for Affiliate status should be reviewed by the Group
Membership Committee and endorsed by the process established by the
Group.

2)  In category 2, institutions which do not have either geographic
proximity to a Main Member or can not find a Main Member sponsor may
request to become an Affiliate Member directly through the
Headquarters/Operations Office.  The patient accrual and record keeping
requirements are identical to those mentioned above for Affiliate
Members in category 1.  Reimbursement for research costs will also
follow the same capitation scheme.  The specific criteria for
determining reimbursement will be the responsibility of the
Headquarters/Operations Office.  Reimbursement will be capped at 30
patients annually in order to encourage Affiliate Members performing at
this high level to seek Main Member status.  On-site auditing will be
the responsibility of the Statistical and Data Management Center, and
must be in accordance with the NCI-CTMB GUIDELINES FOR ON-SITE
MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH
BASES.  All nominations for Affiliate status in category 2 should be
reviewed by the Group Membership Committee and endorsed by the process
established by the Group.  They should also demonstrate quality
record-keeping and strict adherence to all regulatory and human
subjects requirements for clinical trials.  This necessitates that all
category 2 Affiliates have an assurance which is approved by OPRR and
that the IRB is willing to assume responsibility for all the
investigators associated with the Affiliate.  If an Affiliate does not
have an IRB and wishes to make an arrangement with the IRB of another
Affiliate or Main Member, such arrangements must be approved by OPRR.
In addition, all Affiliate investigators who are in private practice
must complete a Non-Institutional Investigator Agreement which is
co-signed by the responsible IRB and is on file at the Group
Headquarters/Operations Office.

Category 2 Affiliates may include:

a)  High Priority Trials Initiative Participants

The High Priority Trials Initiative was implemented by NCI in order to
increase accrual to designated studies by providing financial support
for study-related research to otherwise unfunded investigators.  In
addition, the Office of Cancer Communications, NCI, promotes the
designated trials, and clinical trials research in general, through
public relations activities designed to educate physicians and the
public regarding opportunities to participate in clinical trials
research.  High Priority Trials investigators affiliate with the
Cooperative Group through the Operations Office.  They submit data in
the same format and according to the same standards as any other Member
or Affiliate investigator.  Quality control is assured by the usual
Group monitoring and evaluation procedures.

b)  Minority Initiative Program

CTEP initiated the Minority Initiative Program in 1990 to increase the
accrual of minority patients onto clinical trials and to investigate
the basis for observed differences in cancer outcome among ethnic
groups.  Through this program additional funds are made available to
Cooperative Group headquarters or statistical offices to help support
these goals.  Specific group activities are proposed by individual
Groups and reviewed annually by CTEP.  Activities supported through
this program include capitation awards for increases in minority
accrual, translation of patient education materials into languages
other than English, training for investigators in minority accrual, and
the recruitment of translators and patient advocates to help with
accrual and follow-up of minority patients.

c.  Community Clinical Oncology Program (CCOP) Participants

CCOP participants are funded by the Division of Cancer Prevention and
Control (DCPC).  They are community-based organizations which
participate in Group treatment protocols and cancer control research
studies based in the Groups or in cancer centers.  DCPC periodically
publishes a Request for Applications (RFA) for CCOP funds in which the
application process, eligibility and funding criteria are described.
CCOP participants affiliated with a Cooperative Group have access to
Group protocols approved by and for CCOP accrual and submit data in the
same format and according to the same standards and are audited as any
Main or Affiliate  Members.  Group operations/statistics offices are
funded by DCPC through separate research base awards to support the
additional administrative responsibilities for and analysis of the data
supplied by CCOP members.  Duplicative funds should not be requested in
applications to be funded by DCT.

C.  Scientific/Administrative Considerations

Definitive clinical trials should usually constitute the major portion
of a Group's activities; they should always serve as the ultimate goal
of preliminary developmental trials.  It is essential that important,
original, and feasible treatment questions be posed, that study
questions be answerable in a reasonable period of time, and that the
methodology of each study be sound.  Proper integration of diagnostic
or other support modalities is essential, with standards of quality
control as rigorous as those applied to treatment modalities.

It is anticipated that decisions in all Group activities will be
reached by consensus of the collaborating investigators under the
leadership of the Cooperative Group Chairperson.  Studies will be
conducted in accordance with the CLINICAL TRIALS COOPERATIVE GROUP
PROGRAM GUIDELINES, the INVESTIGATOR'S HANDBOOK, the GUIDELINES FOR THE
CONDUCT OF INTERGROUP STUDIES, and the NCI-CTMB GUIDELINES FOR ON-SITE
MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH
BASES.

In most Groups the process of study generation begins at the level of
a disease or modality committee, which develops specific experiments
ultimately embodied in Group protocols.  This proven organizational
approach provides a forum for investigators who share a common area of
interest, and an arena in which various ideas must compete if they are
to gain the status of a Group study.

The Group and its research committees should develop, articulate, and
follow a comprehensive research plan which summarizes the Group's
specific objectives and lines of investigation for each disease or
modality that it chooses to study.  The purpose of this plan is to
focus attention on long-term goals, and to aid the Group in
prioritization of competing research ideas.  The plan will frequently
include small developmental/pilot studies, Phase II studies, as well as
large-scale Phase III efforts, all designed to take advantage of the
Group's experience, expertise, resources, and clinical opportunities.
These comprehensive research plans for each disease and/or modality
committee will be a major focus of the peer review process.

The multi-center nature of Group trials presents a variety of
challenging methodologic problems regarding assurance of quality and
consistency in study conduct.  The need for formal mechanisms of
medical review and quality control is obvious and Groups have developed
a number of approaches to these issues. Quality control are a complex
topics spanning the entire range of diagnostic and therapeutic
modalities employed by each Group.  Generalization concerning optimal
quality control is impossible.  Cost and benefit are obviously
important factors in this assessment.  Examples of the kinds of
considerations to be applied follow:

1.  Radiation therapy quality control may involve either simultaneous
(rapid turnaround) or retrospective review of port films and compliance
with protocol-specified doses for individual patients.  Minimal
standards for acceptability of equipment may be required.  Each
radiation therapy facility that treats patients on Group studies
undergoes periodic physics review and equipment calibration by the
Radiological Physics Center (RPC).  The RPC in Houston, TX has supplied
each Group's radiation therapy quality control office with the physics
data necessary to conduct its case-level review.

2.  Chemotherapy quality control is usually carried out through
retrospective review of submitted flow sheets, with determination of
protocol compliance in dose administration and dosage modification.
The criteria vary considerably from study to study and from Group to
Group and depend heavily on the specific research questions addressed.

3.  Surgical quality control includes assessment by surgeons of the
adequacy of protocol-specified surgical procedures through review of
the operative notes, study-specific surgical forms, and pathology
reports.  Standards of acceptability for specialized surgical
equipment, or requirements for participation in workshops may be
necessary in some instances.  Where appropriate, surgical modality
committees may wish to draft handbooks of acceptable guidelines for
surgical procedures used in studies.

4.  Pathology review is usually retrospective and may be either by a
committee within the Group or by an external reference panel.
Pathology review is not required by CTEP for all cases, but should be
required by the Group when known variability in the accuracy of
histologic diagnosis is a potentially serious problem or when pathology
data may provide important prognostic information.

5.  Appropriate quality control for other therapeutic and diagnostic
modalities are as essential to good data quality as those described
above. Standardization of decentralized laboratory procedures (e.g.,
hormone receptor determinations) is an important case in point.

6.  Assuring the safety of individual patients participating in each
study, in maximizing their likelihood of exposure to optimal treatment,
and in general, ensuring that the interests of patient participants are
not subsidiary to those of the scientific investigation is critical to
Group science.  The continual assessment of the progress of studies
necessary to achieve these ends is referred to in this document as
study monitoring.  All clinical treatment research carries with it the
obligation to ensure optimal therapy for participating patients, and
optimal conduct of the research such that the patients' participation
is meaningful.  In this context accurate and timely knowledge of the
progress of each study is a critical Group responsibility and includes
the following:

a.  Precise tracking of patient accrual to individual studies by Main
Member or Affiliate site and the mechanisms to ensure adherence to
defined accrual goals;

b.  Ongoing assessment of patient eligibility and evaluability and
correction of specific problems in this regard;

c. Adequate measures to ensure timely submission of protocol-required
data for individual patients;

d.  Adequate measures to ensure timely medical review and assessment of
these individual patients' data;

e. Rapid reporting of treatment-related morbidity in individual
patients and measures to ensure communication of this information to
all parties to whom it is important, including the NCI and the Group
Data and Safety Monitoring Committees;

f.  Prompt assessment of the significance of such information in the
context of the entire study's experience;

g.  Interim evaluation and consideration of measures of outcome
(although to the extent consistent with patient safety and good
clinical trials practice such interim analyses should be minimized in
frequency; access by participating investigators to interim outcome
data should be limited as much as possible.)

7.  Quality Control and On-site auditing

A related need is for verification of the accuracy of data submitted
from individual investigators to the Group.  This need overlaps
considerably with the obligation of the DCT as a sponsor of
investigational agents to ensure visits to each site where
NCI-sponsored clinical trials are performed, for the specific purpose
of: a) auditing medical records, and b) assuring compliance with
regulatory requirements of the Food and Drug Administration (FDA),
including appropriate storage and handling of investigational agents.
Each Group is therefore required to establish a system of periodic
on-site audits of each Main Member/Affiliate, with CTEP oversight of
the audit program.  This dual responsibility of the Groups and the DCT
is referred to as the on-site audit program.  (see the NCI-CTMB
GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE
GROUPS AND CCOP RESEARCH BASES.

a.  Regulatory Obligation

As a sponsor for investigational new agents, the DCT is required by FDA
regulations to maintain an on-site audit program.  Through formal
agreements with the FDA, the DCT has delegated much of this
responsibility to the Groups, although CTEP oversees the program.  The
specific purposes of the audit programs are to document the accuracy of
data submitted to the Group, and to verify investigator compliance with
the regulatory requirements for all clinical investigations.

b.  Data Verification/Protocol Compliance

By comparison of submitted data with information contained in the
patient's actual medical records, this component of the on-site audit
program seeks to assure accuracy and completeness of Group information
integral to the assessment of:

o  Patient eligibility;
o  Compliance with protocol-defined therapy;
o  Endpoint evaluation
o  Treatment related toxicity;
o  Protocol-required laboratory and diagnostic evaluations;
o  Overall quality of record keeping;
o  Concomitant therapy or other information which might affect study
results but is not recorded on submitted study forms.

c.  Regulatory Requirements

This component of the on-site audit program is intended to assess:

o  Documentation of Institutional Review Board (IRB) approvals,
reapprovals, and protocol amendments;

o  Documentation of an IRB-approved, properly signed and dated informed
consent document for each case audited, that includes an adequate
description of the rules and benefits as contained in the model
informed consent submitted to the NCI;

o  Security of investigational drug handling;

o  Adequacy of NCI drug accountability records (DAR).

d.  Procedures

The Group must establish and follow an on-site audit program and audit
procedures, in accordance with NCI-CTMB GUIDELINES FOR ON-SITE
MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH
BASES.  Each Main Member and designated Affiliate must be visited at
least once every 36 months but remains at yearly risk of an audit.
Audits are conducted by peer investigators within the Group.  A
percentage of Main Members/Affiliates are co-site visited by CTEP
Quality Assurance staff or their agents.  Protocols to be reviewed are
selected by the Group in accordance with the above guidelines.  A
sample of investigational agent studies is always included when the
Main Member or Affiliate has accrued patients to such studies.
Individual cases are then randomly selected by the statistical office
for review.

A preliminary report must be faxed to CTMB within one working day of
the audit.  A final report of each audit is sent by the Group to CTMB
within ten weeks of the audit.  CTMB staff review the audit findings as
well as the Group's evaluation and response.

e.  Group Evaluation and Response

The discovery of actual fraud or other serious research misconduct
during a Group audit has been rare.  However, problems covering a wide
spectrum of severity and type are often found; most are appropriately
dealt with by constructive suggestions and are usually remedied through
education of investigators and data managers.  Notification of NCI is
required in the event of findings suggestive of intentional
misrepresentation of data and/or disregard for regulatory safequards,
as well as other matters of sufficient seriousness.  In such instances,
the NCI/CTMB staff should be notified by telephone immediately, since
other Federal agencies may require notification.  Procedures for
immediate suspension of accrual at the Main Member/Affiliate may be
required.

After reviewing the audit report and the Group's response, the CTMB
staff may recommend further action to the Group or the NCI may take
action independently.  In cases of suspected fraud or other serious
problem of compliance with regulatory requirements, CTEP may request
formal investigation by the Office of Research Integrity (ORI, PHS,
DHHS) or the Office for Protection from Research Risks (OPRR, NIH).

f.  Data and Safety Monitoring Committees

For Phase III trials, the NCI has required the Groups to establish Data
and Safety Monitoring Committees (DSMCs) that are independent of study
leadership, are clearly free of conflicts of interest, and have
formally documented policies and procedures which are approved by NCI.
The main objectives of the independent DSMC are to:

1)  Ensure that patients in the trial are protected and that their
interests are not made secondary to the interests of scientific
investigations.

2)  Ensure that evaluation of interim results and decision-making about
continuation, modification, termination of accrual and reporting of
results are made competently based on thorough evaluation.

3)  Ensure that the credibility of trial reports and ethics of trial
conduct are above reproach with no actual or possible appearance of
professional or financial conflicts of interest.

4)  Enable physicians entering patients to remain free of knowledge of
interim efficacy and toxicity data.  This permits physicians to
continue to approach their patients honestly and avoids the need to
modify informed consent based on non-statistically-significant interim
results.

5)  Enable study leadership to remain free of knowledge of interim
efficacy and toxicity data so that they may deal honestly with their
peers in encouraging them to enter patients in the study and so that
they do not put themselves, or the study, at risk by indirectly
divulging interim results.

SPECIAL REQUIREMENTS

The research goals described in this RFA are part of a larger program
of investigational agent development in the NCI.  Each of the CTEP
staff and CTEP Branches listed in the terms and conditions of award
have very specific and well defined responsibilities in terms of
investigational agent development and the role of DCT as a drug sponsor
as defined in CFR 21 Part 312.  The clinical development of new
anticancer agents is a highly important utilization of Group resources,
when carried out as a component of an overall strategy for study of a
given disease.  The Groups are a vital component of the research
apparatus necessary for the clinical development of the many new
investigational agents sponsored by the DCT.

The DCT responsibilities for this development are shared by all
Branches of CTEP.  The Investigational Drug Branch (IDB) is responsible
for 1) planning within CTEP and with members of the extramural
community overall strategies for new agent studies in specific tumor
types; and 2) coordinating and monitoring the trials of new agents
developed by the DCT.  The Pharmaceutical Management Branch (PMB)
provides for the distribution of investigational new agents for which
DCT is the sponsor.  The Regulatory Affairs Branch (RAB) maintains
close contact and ongoing dialogue with the pharmaceutical industry and
with the Food and Drug Administration in order to ensure that new agent
development complies with Federal regulations and proceeds in a
coordinated way.  The Clinical Investigations Branch (CIB) is involved
in prioritizing evaluations of investigational agents compared to
alternative research questions.  The Biometric Research Branch (BRB)
assesses proposed designs for evaluating the benefits of
investigational agents.  The Clinical Trials Monitoring Branch (CTMB)
verifies adherence by the Groups to the quality assurance procedures of
investigational agent trials.  The Office of the Associate Director
(OAD) integrates the efforts of the Branches.

Terms and Conditions of Award

These special Terms of Award are in addition to and not in lieu of
otherwise applicable OMB administrative guidelines, HHS Grant
Administration Regulations at 45 CFR Parts 74 and 92, and other HHS,
PHS, and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is a
cooperative agreement (U10), an "assistance" mechanism (rather than an
"acquisition" mechanism) in which substantial NIH scientific and/or
programmatic involvement with the awardee is anticipated during
performance of the activity.  Under the cooperative agreement, the NIH
purpose is to support and/or stimulate the recipient's activity by
involvement in and otherwise working jointly with the award recipient
in a partner role, but it is not to assume direction, prime
responsibility, or a dominant role in the activity. Consistent with
this concept, the dominant role and prime responsibility for the
activity resides with the awardee(s) for the project as a whole,
although specific tasks and activities in carrying out the studies will
be shared among the awardees and the NCI Program Staff.

A.  Awardee Rights and Responsibilities

The awardee's programmatic responsibilities for the conduct of the
research supported by this cooperative agreement are described in the
CLINICAL TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES; the
INVESTIGATOR'S HANDBOOK, (a Manual for Participants in Clinical Trials
of Investigational Agents Sponsored by the Division of Cancer
Treatment, National Cancer Institute);  and the NCI-CTMB GUIDELINES FOR
ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP
RESEARCH BASES, and any subsequent modifications of these documents.
Specific portions of these documents, as enumerated in the following
sections, are incorporated by reference as terms of award.  These
documents are available from the Cancer Therapy Evaluation Program
(CTEP) upon request.

Throughout these Terms and Conditions of Award "Participant" refers to
all awardees as well as all institutions and/or individual
investigators, both funded and unfunded, with whom they are
participating or collaborating.

1.  Development of Cooperative Group Research Agenda and Protocols

It is the responsibility of the Cooperative Group (henceforth termed
the Group) in accordance with its constitution, bylaws, policies and
procedures to develop the details of the research design, including
definition of objectives and approaches, planning, implementation,
analysis, and publication of results, interpretations and conclusions
of studies.  The Group shall, with CTEP assistance, develop Group
research goals in accord with national research goals and develop
protocols for clinical cancer research in accord with the Group's
research interests, abilities and goals.  The Group Chairperson shall
designate other Group investigators to serve as Protocol Chairpersons
for each proposed study.  Protocols will be developed in accordance
with the instructions in the CLINICAL TRIALS COOPERATIVE GROUP PROGRAM
GUIDELINES, and the INVESTIGATOR'S HANDBOOK.  The INVESTIGATOR'S
HANDBOOK is reference handbook for all investigators who use
DCT-sponsored investigational agents in their clinical trials,
irrespective of funding mechanism.  The INVESTIGATOR'S HANDBOOK
describes, in accordance with NCI-FDA agreements:

o  Requirements for Protocol Development and Submission
o  Ordering Investigational Drugs from NCI
o  Responsibility for Reporting of Results to CTEP
o  Adverse Event Procedures
o  Accountability and Storage of Investigational Drugs
o  Monitoring and Quality Assurance

2.  Coordination of Group Activities

In accordance with the Group constitution, bylaws, policies and
procedures, the Group Headquarters (or Statistical/Data Management
Office as appropriate), under the leadership of the Group Chairperson
and with CTEP assistance, is responsible for coordinating protocol
development, protocol submission, study conduct, quality control and
study monitoring, drug ordering, data management, statistical analysis,
protocol amendments/status changes, adherence to requirements regarding
investigational drug management and Federally mandated regulations, and
protocol and performance reporting.  All the scientific and
administrative decisions related to the Group funded activities and
made by the participating institutions will be coordinated by the Group
Chairperson with the assistance of the staffs of the Headquarters,
Statistical Office, and/or Data Management Office.  The Group
Chairperson or designee will be responsible for communication with the
appropriate CTEP staff.

3.  Protocol Submission

Prior to protocol implementation, the Group Headquarters, under the
leadership of the Group Chairperson, will submit the protocols for
review to CTEP, or its designated Contractor, in accordance with the
instructions in the NCI's INVESTIGATOR'S HANDBOOK and the CLINICAL
TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES.  It is required that all
Phase III protocols be preceded by Concept Review letter describing the
hypothesis to be investigated, the general design of the contemplated
trial plus relevant information on accrual capabilities to document
feasibility.  A letter of intent (LOI) must be submitted for all Phase
II trials that include a DCT investigational agent. These two
mechanisms for preliminary review are required to expedite protocol
development and implementation and to facilitate agreement on study
priority and design (see the INVESTIGATOR'S HANDBOOK, pp32-35, for
further discussion of these mechanisms).

The Group Chairperson, with the assistance of the Group Headquarter's
staff, will communicate the results of the NCI review of protocols to
the participating institutions.

4.  Group Compliance with Federally Mandated Regulatory Requirements

The Group must be in compliance with all Food and Drug Administration
(FDA) regulatory requirements for studies involving investigational
agents and NIH policies applying to the conduct of research involving
human subjects.  These regulations include but are not limited to Title
21 CFR 50,56 and 312 and Title 45 CFR 46.  Participants are required to
follow established Group procedures for complying with the Federally
mandated regulations.

a.  The Group must be able to demonstrate that each participant has a
current approved assurance number on file with the NIH Office for
Protection from Research Risks (OPRR).

b.  The Group must be able to demonstrate that each protocol and
informed consent is approved by the responsible Institutional Review
Board (IRB) prior to patient entry, and that each investigator has a
current FDA Form 1572 and curriculum vitae on file with the
Pharmaceutical Management Branch, (PMB), CTEP.

c.  The Group must be able to demonstrate that each patient (or legal
representative) gives written informed consent prior to entry on study.

d.  The Group must assure timely reporting of all serious and
unexpected toxicities to CTEP.

e.  The Group must establish and maintain an on-site audit program in
compliance with the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF
CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES.

f.  The Group must have a method of providing, upon CTEP request,
summary efficacy and toxicity data to be included in DCT's annual
report to the FDA for each investigational agent.

g.  The Group must implement the CTEP requirements for storage and
accounting for investigational agents provided under DCT sponsorship.

5.  Investigational Drug Management

Investigators performing Group trials are expected, in cooperation with
the NCI, to comply with all FDA monitoring and reporting requirements
for investigational agents.  When new avenues of cancer therapy
involving investigational drugs are pursued, the clinical information
should be acceptable to the FDA for inclusion in a new drug application
(NDA).

6.  Quality Control and Study Monitoring

a.  The Group shall establish and implement mechanisms for quality
control of therapeutic and diagnostic modalities employed in its
trials.  Participants are required to follow Group procedures for
quality control.  Quality control at a minimum should consist of:

1)  Pathology: Verification of pathologic diagnosis in cases where
known variability in the accuracy of histologic diagnosis is a
potentially serious problem and where pathology data may provide
important prognostic information.

2)  Radiation Therapy:  Review (either concurrent or retrospective) of
port films and compliance with protocol-specified doses for individual
patients. Determination of adequacy of radiation delivery with
assistance of the Radiological Physics Center (RPC), whose functions
usually include equipment dosimetry, periodic institutional visits and
other aspects of physics review.

3)  Chemotherapy:  Review of flow sheets with determination of protocol
compliance in dose administration and dosage modification.

4)  Surgery:  Assessment of adequacy of protocol-specified surgical
procedures through review of operative notes and study-specific
surgical forms.

b.  The Group shall establish and implement mechanisms for study
monitoring and quality assurance.  Participants are required to follow
Group procedures for study monitoring.   The Group is responsible for
assuring accurate and timely knowledge of the progress of each study
through:

1)  tracking and reporting of patient accrual and adherence to defined
accrual goals;

2)  ongoing assessment of case eligibility and evaluability;

3)  timely medical review and assessment of patient data;

4)  rapid reporting of treatment-related morbidity and measures to
ensure communication of this information to all parties;

5)  interim evaluation and consideration of measures of outcome as
consistent with patient safety and good clinical trials practice;

6)  timely communication of results of studies; and

7)  an on-site monitoring program.

The awardee is responsible for ensuring that all Main Members and
Affiliates have routine audits in accordance with the NCI-CTMB
GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE
GROUPS AND CCOP RESEARCH BASES and that the results of audits are
reported to the NCI in accordance with the guidelines.  In the event
that the NCI determines that the awardee failed to comply with these
guidelines, the accrual of new patients to the Group's protocols at the
affected Main Member/Affiliate shall be suspended immediately upon
notice of the NCI determination.  The suspension will remain in effect
until the awardee conducts the required audit and the audit report or
remedial action is accepted by the NCI.

The awardee will be responsible for notifying any affected Main
Member/Affiliate of the suspension.  During the suspension period, no
funds from this award may be provided to the Main Member/Affiliate for
new accruals, and no charges to the award for new accruals will be
permitted.  The NCI will also notify an institution that is the direct
recipient of a cooperative agreement from the NCI if it is necessary to
suspend accrual at that institution or at a third party institution
supported under that institution's cooperative agreement.

c.  Quality Assurance and Quality Control of Data

The awardee must follow NCI-approved procedures developed by the Group
for the prevention and/or identification of false or otherwise
unreliable data and for quality assurance of data collected by the
Group.  The awardee must follow Group procedures for the assurance of
data quality and quality control in accordance with Group guidelines
and NCI policies.

In the event that there is a finding through the quality assurance
and/or quality control programs of any indication of a pattern of
non-compliance with protocol or regulatory requirements or a finding of
possible alteration of data, these findings must be reported in
accordance with the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF
CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES.

The awardee must follow policies developed by the Group and approved by
the NCI for auditing the accuracy of scientific data submitted by Group
participants.

7.  Data Management and Analysis

The Group shall establish and implement mechanisms for data management
and analysis that ensure that data collection and management procedures
are:  (a) adequate for quality control and analysis; (b) as simple as
appropriate in order to encourage maximum participation of physicians
entering patients and to avoid unnecessary expense; and (c)
sufficiently uniform across Groups. Participants are required to follow
Group procedures for data management and analysis.

8.  Data and Safety Monitoring Committees

The Group must establish and maintain a Data and Safety Monitoring
Committee (DSMC) for Phase III clinical trials.  The policies and
procedures of the DSMC must be approved by the NCI.  The Group must
comply with the approved policies and procedures of the DSMC.

9.  Protocol Closure

The Group shall establish and implement mechanisms for interim
monitoring of results and monitoring protocol progress.  If the Group
wishes to close accrual to a study prior to meeting the initially
established accrual goal, the interim results and other documentation
should be made available to NCI staff for review and concurrence prior
to implementation of the decision by the Group.  It is recommended that
statistical guidelines for early closure be presented as explicitly as
possible in the protocol in order to facilitate these decisions.  In
the event that the DSMC has recommended early closure, DSMC procedures
regarding notification of CTEP must be followed.

10. Protocol Reporting Requirements

Reporting requirements will be in agreement with FDA regulations and
NCI procedures.  Interim reports of each activated and ongoing study
shall appear in the minutes of each Group meeting and shall include
specific data on patient accrual as well as, when appropriate, detailed
reports of treatment-associated morbidity.  Quarterly accrual
information must be provided by the Headquarters or Statistical Office
as appropriate to NCI for all active studies.  A system for providing
such information in a timely manner should be in place.  Participants
must provide accrual data to the Group in accordance with Group
procedures.

11.  Adverse Event Procedures

In order to be in compliance with FDA regulations, all recipients of
NCI support for clinical trials, including Groups responsible for
coordinating and monitoring such trials, must promptly notify the NCI
and any other sponsors of the trial of adverse events (i.e., adverse
drug reactions) according to directions provided in the adverse event
reporting section of the protocol.

The awardee will notify all institutions/investigators participating in
this project, funded or unfunded, about the above requirement and about
the institutions'/ investigators' responsibility to report adverse
events as specified in the protocol.

The awardee will promptly notify the Investigational Drug Branch (IDB)
Drug Monitor for DCT-sponsored investigational agents and the NCI
Program Director for other agents, of serious or life-threatening
events, as instructed in the protocol.

12.  Performance Review

The Group shall establish and follow policies and procedures for
credentialling participating institutions and conducting periodic
review of the performance and membership status of each Main
Member/Affiliate.  This review should examine scientific contributions,
patient accrual, data accuracy and timeliness, protocol compliance,
long-term patient follow-up and audit results.  This mechanism will
include a procedure for the Group Chair to recommend an adjustment of
funds within the Group as appropriate for the level of participation in
Group activities, including (but not limited to) accrual. This
procedure can be either prospective (i.e., reimbursement by the case)
or retrospective (financial adjustment at the time a non-competing
continuation [Type 5] award is made).

13.  Procedures in the Event of Scientific Misconduct

If a duly authorized governmental or institutional body issues a final
determination that scientific misconduct has occurred or if the awardee
determines that other events have occurred which have significantly
affected the quality or integrity of the Group data or patient safety,
the awardee is responsible for notifying the Group Data and Safety
Monitoring Committee (DSMC), the CTMB, the collaborating investigators,
the appropriate Institutional Review Boards (IRBs), and other sponsors
of the affected work.

The awardee is also responsible, if the events described above have
occurred, for ensuring that submitted but unpublished abstracts and
manuscripts are corrected, if possible.  If publication deadlines have
passed or if abstracts and/or manuscripts containing the affected data
have already been published, the awardee is responsible, within 90 days
after learning of the event(s) significantly affecting the quality of
the Group data or patient safety, for submitting to NCI a re-analysis
of the results deleting the false or otherwise unreliable data, and
disclosing within the text the reason(s) for the reanalysis.  The
awardee must submit the reanalysis for publication.  The NCI may
disseminate information about the reanalysis as broadly as it deems
necessary.

The awardee must use its best efforts to notify all scientists,
research laboratories, and other organizations to which the awardee has
sent research materials affected by false or otherwise unreliable data.

True copies of data files and other supporting documentation from
studies affected by scientific misconduct or other findings affecting
the quality or integrity of data or patient safety shall be made
available to the NCI in a timely manner upon the request of the Grants
Management Officer, NCI.  The NCI reserves the right to reanalyze, to
publish, or to distribute its analyses of these data when it is in the
interest of public health.  Prior to release, publication or
distribution of such analyses, the NCI will provide such analyses to
the awardee.

14.  Data Files Available to NCI Upon Request

Upon the request of the Grants Management Officer, NCI, true copies of
data files and supporting documentation for all NCI-supported protocols
that have a major impact on patterns of care, as determined by the NCI,
shall be made available to the NCI in a timely manner.

15.  Notification of Patients by the Awardee During Patient's Lifetime

In order for there to be an appropriate response in the event the NCI
determines, either while a protocol is active or (if relevant) during
the lifetime of the subjects following protocol closure, that a
medically important toxicity or side effect is associated with
protocol-directed treatment or that the medical care of one or more
subjects may have been compromised by scientific misconduct or other
finding affecting the integrity of the data or patient safety at the
awardee institution or at a third-party institution, funded or
unfunded, the awardee shall assure that the institution(s) responsible
for these subject(s') accrual, whether funded or unfunded, will have
procedures in place to: (i) contact each subject individually at his or
her last known address on file with the institution and which give each
subject contacted appropriate information and the right to communicate
with an appropriate institutional representative and, in the event of
misconduct, to meet with a physician not connected with the clinical
trial or study in which the subject has participated; and (ii)
encourage subjects to notify the institution of any changes of address.
The procedure must provide for informing the subjects fully of: the
consequences of the toxicity or misconduct for their care and
well-being, if any, and the availability of follow-up; and their
opportunity to examine any portion of their medical records relevant to
the potential effect of the toxicity or side effect upon them or that
may be affected by scientific misconduct or other findings affecting
the quality or integrity of the data or patient safety.

It is understood that under regulations at 45 CFR Section 74.53, NCI
has a right of access to research records pertinent to the NCI funding.
In exceptional circumstances, such as a public health emergency, the
institutions will be required to provide subject names and treatments
to the NCI in a format which allows direct notification of the patient
by the NCI.

16.  Progress Reporting

Annual progress reports will be submitted to the NCI in accordance with
the instructions in the CLINICAL TRIALS COOPERATIVE GROUP PROGRAM
GUIDELINES.

B.  NCI Staff Responsibilities

The role of the Cancer Therapy Evaluation Program (CTEP) staff as
described throughout these terms and conditions of award is to assist
and facilitate but not to direct research activities.  This cooperative
agreement is part of a larger program of investigational agent
development in the NCI.  Each of the CTEP staff listed below has very
specific and well defined responsibilities in terms of investigational
agent development and the role of DCT as a drug sponsor as defined in
CFR 21 Part 312.

1.  Scientific Resource for NCI-Supported Clinical Investigations

The NCI Program Director, the Associate Director, CTEP (AD, CTEP), and
staff of the Clinical Investigations Branch (CIB), the Investigational
Drug Branch (IDB), the Biometric Research Branch (BRB), the Regulatory
Affairs Branch (RAB), the Pharmaceutical Management Branch (PMB) and
the Clinical Trials Monitoring Branch (CTMB) will serve as resources
available to Cooperative Groups for specific scientific information
with respect to treatment regimen, clinical trial design,
investigational agent management and regulatory issues. The CIB Senior
Investigator(s) designated by the NCI Program Director will assist the
Group as appropriate in developing information concerning the
scientific basis for specific trials and also will be responsible for
advising the Group of the nature and results of relevant trials being
carried out nationally or internationally.  The CIB Senior
Investigators and IDB Drug Monitors will also provide updated
information on the efficacy and toxicity of investigational new agents
supplied to Group members under an Investigational New Drug (IND)
Application sponsored by the Division of Cancer Treatment (DCT).  The
CIB Senior Investigator will advise the Cooperative Groups of potential
studies which will be relevant to new avenues of cancer therapy.

2.  Protocol Development

A protocol is the detailed written plan of a clinical experiment.  The
protocol must be mutually acceptable to the Group and to the CTEP
Protocol Review Committee (PRC).  Communication with CTEP staff at the
various stages of protocol development is encouraged.  The CIB Senior
Investigator will assist the Group in protocol design as may be
appropriate by providing information regarding:  (a) the existence and
nature of concurrent clinical trials in the area of research, pointing
out possible duplication of effort, (b) information including relevant
pharmacokinetic and pharmacodynamic data concerning investigational
agents, and (c) availability of investigational agents, including
biologic response modifiers.  The CIB Senior Investigator will also
comment on the scientific rationale and value of the proposed study,
the design, the statistical requirements, and the implementation of the
study, if indicated.

CTEP staff will review and provide a Program response through the AD,
CTEP, to Concepts for Phase III protocols and Letters of Intent for
Phase II protocols, commenting on study originality and programmatic
interest.  These two mechanisms for preliminary review are required to
expedite protocol development and implementation and to facilitate
agreement on study priority and design (see the "INVESTIGATOR'S
HANDBOOK," pp32-35, for further discussion of these mechanisms).

3.  Review of Proposed Protocols

Group protocols will be reviewed by the CTEP Protocol Review Committee
(PRC) which will meet weekly.  It will be chaired by the AD, CTEP or
his/her designee.  Ad hoc reviewers, external to NCI, will be utilized
when deemed appropriate by the committee chairperson.  Formal protocol
review and CTEP approval prior to activation are required for the
following types of studies: (a) all protocols utilizing DCT resources
and investigational agents regardless of IND-sponsor; (b) all protocols
that permit entry of one hundred or more patients; and (c) all phase
III protocols.  Other protocols will be filed with CTEP for information
purposes but will not require CTEP approval. Advisory reviews of such
protocols may be provided to the Group at CTEP's discretion.  For all
protocols that require review, the AD, CTEP will provide the Group with
a consensus review that describes recommended modifications and other
suggestions, as appropriate (see the Investigator's Handbook," pp
43-47, for further information regarding protocol review at CTEP).

The major considerations relevant to Protocol Review by CTEP include:
(a) the strength of the scientific rationale supporting the study, (b)
the medical importance of the question being posed, (c) the avoidance
of undesirable duplication with other ongoing studies, (d) the
appropriateness of study design including interim monitoring plans, (e)
a satisfactory projected accrual rate and follow-up period, (f)
patient safety, (g) compliance with Federal regulatory requirements,
(h) adequacy of data management, (i) appropriateness of patient
selection, evaluation, assessment of toxicity, response to therapy and
follow-up.

If a proposed protocol is disapproved, the specific reasons will be
communicated to the Group chairperson as a consensus review within 30
days of protocol receipt by the NCI.  NCI will not provide
investigational drugs or permit expenditure of NCI funds for a protocol
that it has not approved.  The CIB Senior Investigator will be
available to assist the Group in developing a mutually acceptable
protocol, consistent with the research interests, abilities and
strategic plans of the Group and of the NCI.

4.  Review of Quality Control and Study Monitoring

The CTMB staff, will review and provide advice regarding mechanisms
established by the Group for quality control of therapeutic and
diagnostic modalities employed in its trials.    The CTMB staff will
review and approve the mechanisms established by the Group for study
monitoring including the Group's on-site auditing program.

CTEP and/or its contractor staff may attend, as observers, the on-site
audits conducted by the Group.  The frequency of participation by an
NCI representative as observer will be determined by the NCI.

5.  Review of Data Management and Analysis

The BRB staff will review mechanisms established by the Group for data
management and analysis.  When deemed appropriate staff will make
recommendations to ensure that data collection and management
procedures are: (a) adequate for quality control and analysis; (b) as
simple as appropriate in order to encourage maximum participation of
physicians entering patients and to avoid unnecessary expense; and (c)
sufficiently uniform across Groups.  The NCI will have access to all
data although they remain the property of the awardee institution.
Data must also be available for external monitoring as required by
NCI's agreement with the FDA relative to the NCI's responsibility as
drug sponsor.

6.  Data and Safety Monitoring Committees

The NCI Program Director, assisted by the BRB staff will assess Group
compliance with NCI established policies on Data and Safety Monitoring
Committees (DSMCs) for Cooperative Group Phase III trials.  One or more
CTEP staff will serve as non-voting members on the DSMC.

7.  Protocol Closure

The AD, CTEP, may request that a Phase I or Phase II protocol study be
closed to accrual for reasons including:  (a) insufficient accrual
rate; (b) poor protocol performance; (c) patient safety; (d) study
results are already conclusive; and (e) emergence of new information
which diminishes the scientific importance of the study question.

The AD, CTEP, may request that the Group DSMC consider closing a Phase
III protocol to accrual for reasons including:  (a) insufficient
accrual rate; (b) poor protocol performance; (c) patient safety; (d)
study results are already conclusive; and (e) emergence of new
information which diminishes the scientific importance of the study
question.

NCI will not provide investigational agents or permit expenditures of
NCI funds for a Phase I or Phase II study after requesting closure
(except for patients on treatment and follow-up).

8.  Involvement in Investigational Drug Management

The NCI will have the option to cross file or independently file an IND
on investigational agents evaluated in trials supported under
cooperative agreements.  This would apply to drugs not developed in the
NCI drug development program.

The NCI Program Director, assisted by the RAB staff and the PMB staff
will advise investigators of specific requirements and changes in
requirements concerning investigational drug management that the Food
and Drug Administration (FDA) may mandate.

9.  Review of Compliance with Federally Mandated Regulatory
Requirements

The CTMB staff and the RAB staff will review and provide advice
regarding mechanisms established by the Group to meet Food and Drug
Administration (FDA) regulatory requirements for studies involving
DCT-sponsored investigational agents and Office for Protection from
Research Risks (OPRR) requirements for the protection of human
subjects.

10. CTEP attendance at Cooperative Group Meetings

CTEP staff, as designated by the NCI Program Director, will attend the
semi-annual Group meetings and will be invited as a non-voting observer
to Group Executive Committee Meetings.

11.  Facilitate Completion Of Important Trials

CTEP staff will take an active role in promoting the timely completion
of important studies, for example by encouraging and facilitating
Intergroup collaboration when appropriate, or by assisting in the
mobilization of other available and required resources.

C.  Collaborative Responsibilities

1.  Development of Intergroup Trials

The CIB Senior Investigators will conduct disease or modality oriented
strategy meetings for the purpose of jointly developing the DCT
Clinical Trials Cooperative Group Program priorities for future
protocol development.  Group investigators, NCI staff and other
extramural investigators will attend these meetings.  The Groups and
CTEP staff will work together to facilitate the timely development of
protocols resulting from the consensus developed at such strategy
meetings.

2.  Investigational Drug Development

When new avenues of cancer therapy involving investigational drugs are
pursued, the clinical information should be acceptable to the FDA for
inclusion in a New Drug Application (NDA).  In collaboration with NCI
staff, the Group will develop protocols to obtain such information as
needed.

3.  Data Safety and Monitoring Committees

The appropriate conduct of the Group DSMC procedures are a
collaborative responsibility of the Group and CTEP members.

4.  Cooperative Group Chairpersons' Semi-Annual Meetings

The Chairperson of each Cooperative Group, the NCI Program Director,
the CIB Senior Staff, and other NCI personnel as indicated will meet
semi-annually to discuss issues of relevance to the Clinical Trials
Cooperative Group Program.

5.  Cooperative Group Statisticians' Meeting

Each Group's Chief Statistician, the NCI Program Director, the BRB
staff, and other NCI personnel as indicated will meet together annually
to discuss issues of relevance to the Clinical Trials Cooperative Group
Program.

D.  Arbitration

Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), between award recipients and the NCI
may be brought to arbitration.  An arbitration panel composed of one
Group nominee, one NCI nominee, and a third member with clinical trials
expertise chosen by the other two will be formed to review the CTEP
decision and recommend an appropriate course of action to the Director,
DCT.  The arbitration procedures in no way affect the awardee's right
to appeal an adverse determination under the terms of 42 CFR Part 50,
Subpart D, and 45 CFR Part 16. The Group will not expend NCI funds to
conduct any study disapproved by CTEP unless CTEP's disapproval has
been modified by the arbitration process outlined above.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results from
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43)
and supersedes and strengthens the previous policies (Concerning the
Inclusion of Women in Study Populations, and Concerning the Inclusion
of Minorities in Study Populations), which have been in effect since
1990.  The new policy contains some provisions that are substantially
different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which was reprinted in the Federal
Register of March 28, 1994 (59 FR 14508-14513) to correct typesetting
errors in the earlier publication, and reprinted in the NIH Guide for
Grants and Contracts, Volume 23, Number 11, March 18, 1994.
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

LETTER OF INTENT

Prospective applicants for this RFA are asked to submit, by June 23,
1995, a letter of intent that includes a descriptive title of the
proposed research, the name, address, and telephone number of the
Principal Investigator, the identities of other key personnel and
participating institutions, and the number and title of the RFA in
response to which the application may be submitted.  Although a letter
of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains
allows NCI staff to estimate the potential review workload and avoid
conflict of interest in the review.

The letter of intent is to be sent to:

Richard S. Ungerleider, M.D.
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 741
Bethesda, MD  20892
Telephone:  (301) 496-2522
FAX:  (301) 402-0557

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of Grants
Information, Division of Research Grants, National Institutes of
Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-
7762, telephone 301/435-0714; and from the program administrator listed
under INQUIRIES.

The RFA label available in the PHS 398 (rev. 9/91) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time for
review.  In addition, the RFA title and number must be typed on line 2a
of the face page of the application form and the YES box must be
marked.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed, photocopies, in one package to:

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies and all appendix
material must also be sent to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Boulevard
Bethesda, MD  20892
Rockville, MD 20852 (for express mail)

Applications must be received by August 25, 1995.  If an application is
received after that date, it will be returned to the applicant without
review. The Division of Research Grants (DRG) will not accept any
application in response to this RFA that is essentially the same as one
currently pending initial review, unless the applicant withdraws the
pending application.  The DRG will not accept any application that is
essentially the same as one already reviewed.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research.  If so, a letter of agreement from either the GCRC program
director or principal investigator could be included with the
application.

SPECIAL INSTRUCTIONS FOR THE PREPARATION OF COOPERATIVE GROUP
APPLICATIONS

A.  Inclusion of Women and Ethnic Minority Individuals in Leadership
Positions

The NCI encourages applicants for these cooperative agreements to
include women and members of U.S. ethnic minority populations in
positions of leadership in the Group structure.

B.  Application Preparation

All applications must be submitted on the form PHS 398 (rev. 9/91).
Successful applications for each Group component
(Headquarters/Operations Office, Statistical and Data Management
Center, and Main Member) will be awarded as separate cooperative
agreements to the sponsoring institutions and will include the Terms
and Conditions of Award specified in this RFA.

Each individual application must contain a detailed budget for the
first 12-month period and a budget for the entire proposed project
period for direct costs.

All applications, including that of the Headquarters/Operations Office,
the Statistical and Data Management Center, and the Main Members should
describe the scientific and administrative experience of key personnel
and should include and follow the PHS Form 398 instructions for
Biographical Sketches and Other Support information.

On page 2 of the PHS 398 form, in the section entitled PERSONNEL
ENGAGED ON PROJECT, it is imperative that all applicants list all
individuals and their institutions participating in the scientific
execution of the project in the format as specified including those
with no requested salary support.  All applicants must ensure that the
list is complete using as many continuation pages as necessary.

The key feature of this RFA is that it requires a
Headquarters/Operations Office application to be submitted by a Group
Chairperson that lists the Main Members and Statistical and Data
Management Center as integral components of the Group.  All Main
Members seeking cooperative agreement funding must submit a separate
application identifying the Group with which they are collaborating.
The Statistical and Data Management Center application must be
submitted separately, and must also identify the
Headquarters/Operations Office with which it is affiliated.

For each Cooperative Group being proposed, the specific application
requirements are listed below:

1.  Headquarters/Operations Office

The essence of a Group's program of clinical trials should be described
in the application for support of its Headquarters.  The application
should characterize the Group's mission, its plans to accomplish that
mission, and present evidence of research accomplishments by the
Group's scientific leadership.  It should specify concrete research
proposals in breast and bowel cancer.  It should outline the Group's
strategy for each disease or modality, including rationale and future
plans; a clear sense of direction should be evident.  In addition to
its scientific proposals, the Headquarters application should also
contain information describing the Group's organizational structure,
and the operating procedures and policies to accomplish major Group
objectives and responsibilities.

a.  Research Plan

The following format is suggested for following items 1-4 of the
"Research Plan" section of the standard PHS Form 398 instructions.

1)  Major Research Objectives - This section should concisely describe
the Group's several major research objectives.  This section should
include plans for the inclusion of women and minorities as research
subjects in Group studies.

2)  Group Organizational Structure - This should include a clear
description of the formal organizational structure of the Group,
including lines of authority and responsibility, with particular
attention to the relationship of the organizational structure to the
Group's major objectives.  The organizational structure will usually
include a number of disease, modality, and administrative committees,
in addition to the three major functional components (Headquarters,
Statistical/Data Management Office, and Main Member Institutions).  The
committees will have various research, quality control, and
administrative mandates.  Productive interaction of the organizational
elements should be described and documented.  The proposed members of
the Group's executive committee should be named, along with their
subspecialty affiliations.  Procedures for the selection of Group
leadership should be described.  Procedures for credentialling members,
for review of their performance, and for ranking member institutions in
terms of contributions to the Group, should be described.

3)  Research Strategies - It is essential for the Group and its
research committees to develop and articulate comprehensive plans which
summarize the Group's specific objectives and lines of investigation
for each disease and modality chosen for study.

For each DISEASE COMMITTEE, the application should:

a)  Briefly describe the major scientific goals and strategies of the
committee.

b)  Identify potential protocols which exemplify how the committee
plans to achieve its goals.

c)  Identify and discuss the major research questions relevant to the
purview of the committee.

4)  Quality Control and On-site Auditing - This section should describe
the Group's plans for its programs of quality control and on-site
auditing.  This function will reside in the Statistical and Data
Management Center but should be additionally described in the
Headquarter's application.  The budget request should be in the
Statistical and Data Management Center application.

5)  Group Administration - This section should address the major roles
and responsibilities of the Group administrative staff together with
other matters of relevance to the management of the Group.  It should
describe a system to ensure capable, efficient, and responsible
management by the Group's leadership, as well as ways to identify
problems and proposed solutions. Applications should clearly document
that the proposed Group Chairperson is experienced in dealing with the
problems of cooperative clinical cancer research and that s/he has
appropriate experience to qualify him/her as the Group's leader.

6)  Data and Safety Monitoring Committees - the application should
describe the Group policies and procedures regarding DSMCs.  It should
include proposed membership rosters of the committee(s), and procedures
for avoiding conflicts of interest, such as financial disclosure
procedures.

7)  Group Policies and Procedures - A copy of the proposed Group
Constitution and Bylaws, and a copy of the Group Policies and
Procedures, should be provided as an Appendix to the application.  The
application itself should specifically describe Group policies
regarding conflict of interest issues, the training of Group
investigators, nurses and data managers/clinical research associates
regarding ethics in the conduct of clinical research, and procedures in
the event of scientific misconduct.  The application should document
ongoing ethics training of Group participants, collection of conflict
of interest statements from relevant members, and other efforts to
employ these policies.  At the time of the award, the Grants Management
Specialist may request an additional copy of the Group's Constitution
and Bylaws, and a copy of the Group Policies and Procedures.

b.  Budget

The Headquarters/Operations Office budget should be presented in
logical, discrete units, with specific budgets for each unit as well as
the composite headquarters request.

A separate budget page and item entitled "Developmental Fund" may be
included. The purpose is to provide the Group leadership with resources
to support new initiatives, special high-priority projects, and limited
funding for candidate members.  The first year's plans for this
Developmental Fund must be carefully justified, and the Group's process
for allocating the funds clearly described where relevant.

The following budget guidelines apply specifically to the
Headquarters/Operations Office and Statistical and Data Management
Center budgets; the categories refer to the item entitled "Detailed
Budget for Initial Budget Period" on (Form Page 4) of the PHS Form 398
grant application kit.

1)  Personnel - Precise justification for the amount of effort
requested for each position is essential.

a)  Scientific - research costs include the time and effort involved in
developing the research agenda and repertoire of protocols for the
Group, and analysis and publication of the results of Group research in
peer reviewed journals in a timely manner.

b)  Data Management - research costs include the time and effort
involved in the central collection, computerization and analysis of
primary patient data; determination of eligibility; registration and
randomization; forms development; etc.

c)  Laboratory Investigations - research costs include the time and
effort related to additional laboratory investigations specific to the
research goals of the project, i.e., not associated with conventional
patient care (note: some Cooperative Groups recommend these activities
be allocated by NCI directly, through institutional U10 awards;
nevertheless, their description and justification should be included in
the Headquarters/Operations Office application).

d)  Administrative - research costs include the time and effort
involved in the overall management of the Group's resources, compliance
with regulatory activities, quality assurance and study monitoring
procedures.

2)  Consultant Costs - Reasonable consultant costs are allowed, if the
consultant is contributing directly to the conduct or development of
Group research.  Most of a Group's consultant costs should appear in
the Headquarters budget.  Clear and quantifiable justification is
required.  These costs include travel, per diem and consultant fees, if
applicable and within institutional policy.

3)  Equipment - Justification should include percent of time used for
Group business as well as necessity for purchase.  The amount of funds
requested should be based on the percent of usage. Include only those
equipment items that are required to conduct Group protocols.

4)  Supplies - research costs include those related to communication
and information dissemination among Group participants.  Quantitative
justifications based on actual use should be provided.

5)  Travel - The importance of meetings to the accomplishments of the
Group's research objectives is obvious, as is the necessity to maintain
careful control of the size of this budget item. The budget for travel
must be itemized and justified.  It should include:

o  trips by the Group's leadership and investigators on behalf of the
Group to the NCI and other national organizations where the results of
the Group research must be represented or where Group research
strategies are to be discussed;

o  travel for committee members to committee meetings held separately
from the semi-annual Group meetings;

o  travel for persons on the Headquarters staff who must attend the
Group's semi-annual meetings;

o  a reasonable number of carefully justified trips for provisional or
otherwise unfunded Group members to attend the semi-annual meetings in
order to encourage participation and assure input from all relevant
modalities is also allowable (see above regarding Developmental Fund).

6)  Alterations and renovations - These costs are not allowable in the
Clinical Trials Cooperative Group Program.

7)  Other expenses - research costs include those related to
communication and information dissemination among Group members.
Include here costs of equipment rental and maintenance (copiers,
telephones, computers), postage, copying and printing, etc., justified
quantitatively on the basis of previous experience, where relevant.

8)  Consortium/contractual costs - research costs include support to
Group members who are responsible for committees or laboratory
investigations, for Group members whose institutions do not receive
institutional U10 awards for the research costs related to approved
clinical trials activities, or for patient accrual.  These third party
costs may be presented as consortium arrangements (for substantive
programmatic work), as subcontracts, or as reimbursements based on
formulas.

If third party costs are requested for consortium/contractual
participants, a separate detailed budget page, with appropriate
justification, must be provided for each arrangement.  Indirect costs
to consortium/contractual participants are included in the direct cost
level for the Headquarters. Groups are encouraged to structure their
organization in a manner which minimizes the burden of indirect costs
on the overall Group budget.

Reimbursement for patient accrual is to be based on formulas that must
relate to the institution's membership category, scientific and
leadership contributions, and prior performance including accrual and
assessment of data accuracy and timeliness.  A description of how the
formula was determined, including a line item budget breakdown of the
research costs, must be included in the application.  In addition, the
application must include a plan for disbursement of funds that includes
consideration of performance and quality factors including eligibility
and evaluability rates; data accuracy and completeness; and quality of
on-site audits, etc.  The funds received by Affiliates for patient
accrual should be subject to modification based on results of the
Group's performance reviews.  These costs should be included in the
consortium/contractual costs category of the Headquarter's budget.

Consortium arrangements and all other contractual arrangements,
including all mechanisms for reimbursement for patient accrual, must be
formalized in writing in accordance with applicable Public Health
Service policy requirements (PHS Grants Policy Statement, revised 9/94,
page 8-17).  A statement that the applicant organization and the
collaborating organization have established or are prepared to
establish a formalized agreement that will ensure compliance with all
pertinent Federal regulations and policies must be included in the
application.  Also include all pertinent biographical sketches and a
list of all other support for all relevant consortium participants.

2.  Statistical and Data Management Center Application

The statistical and Data management center is funded via a separate
cooperative agreement. Thus a separate application is required which
should address operational roles and responsibilities discussed under
RESEARCH OBJECTIVES, (B.) Organization.  It should describe in detail
the Group's data management practices and procedures, its quality
control and study monitoring methodology, and its analytical techniques
and resources.

a.  Research Plans

The following format is suggested for following items 1-4 of the
"Research Plan" section of PHS Form 398 instructions.  Wherever
appropriate, narrative should supplement (rather than duplicate or
replace) standard manuals, which should be supplied.

1)  Roles and Responsibilities - list the major objectives of the
Group's statistical and central data management staff.

2)  Organization and Facilities - describe the organization and
facilities to accomplish the complex tasks of central data management,
quality control, study monitoring, and data analysis.

3)  Data Management Policies and Practices - describe the flow of data
following submission from the individual investigator.

4)  Quality Control - describe procedures for quality control and
accuracy verification.

5)  Study Monitoring Procedures  - describe the Group's standard
methods for ongoing study monitoring, including interactions with study
chairs.

6)  Study Design and Data Analysis - describe the Group's routine
methodologic practices (e.g., methods of sample size calculations,
choice of testing and estimation procedures, interim analysis policies,
early stopping procedures, etc.)  Include plans for the inclusion of
women and minorities as research subjects in Group studies.

7)  On-site Audit Program - describe the method by which the Group will
structure, monitor, and regulate this program in conformance with the
NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR
COOPERATIVE GROUPS AND CCOP RESEARCH BASES.  Also, describe the
interactions that will occur with NCI.

8)  Partnership in Group Research - describe the role and contributions
of the Group's statisticians to Group research.  The involvement of
statisticians in designing studies should be documented.

9)  Independent Research - described research being conducted by the
statistical office of the Cooperative Group using Group resources,
including the data base.

b.  Budget

See budget guidelines in this RFA referring to the
Headquarters/Operations Office.  The statistical and data management
center budget should be presented in logical, discrete units with
specific budgets for each unit as well as the total Center's request.

In accordance with the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF
CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES, Groups
are required to conduct routine on-site audits of Main
Members/Affiliates that participate in NCI-supported clinical trials.
Personnel, travel expenses, and computer systems to accomplish this
task must be carefully and fully documented. Budgets shall include
travel for protocol chairs and others who must perform quality control
functions away from their home institution and travel for the on-site
audit program.  Because of the importance of the quality control and
on-site audit program, a separate budget for each function should be
prepared.

3.  Main Member Applications

Each Main Member application should concentrate on the contributions of
the institution to the Group.  Specifically, applications should focus
on the roles and responsibilities defined in RESEARCH OBJECTIVES, (B.)
Organization, Main Member Applications.  The clinical trials and
research strategies of the Group are described in the Headquarters
application, and should not be repeated in the individual institution
applications.  Affiliate investigators associated with primary members
must satisfy Group criteria for participation, and may request funds
from only one source.

Specific assets of the institution regarding access to particular
patient populations should be included in the application.

a.  Research Plan

The following format is suggested for following items 1-4 of the
"Research Plan" section described in the standard form 398
instructions.  Standardized reporting formats across the Group are
strongly advised.

1)  Summarize the institution's cancer research interest and
capabilities.

2)  Describe the potential scientific contributions of the
institution's investigators to the Group, focusing on their roles in
shaping the Group's research strategies and in scientific committee
leadership.

3)  Describe the role of the institution's investigators in chairing or
otherwise managing protocols.

4)  Describe potential institutional pilot studies and other clinical
research contributions to the Group.

5)  Identify core services provided by the institution, such as
laboratory studies or assays for particular protocols, service on
site-visit teams or audits, etc.

6)  Describe the proposed participation by the institution's
investigators in Group administrative committees (e.g., membership,
audit, etc.) with attention to the particular expertise of the
institution's investigators.

7)  Describe institutional procedures for data management and data
submission to the Group.  Particular attention should be given to
management of data from Affiliates.

8)  Describe the organization employed for institutional Group
participation. Document adequate participation from and interactions
among all modalities and disciplines required for conduct of Group
studies.  Describe procedures for determining patients' protocol
eligibility, and for their ongoing treatment once they are entered onto
Group studies.  Describe the process for determining
intra-institutional protocol priorities.

9)  Describe potential problems anticipated in achieving research goals
together with concrete plans designed to address such problems.

10) If relevant, describe the existing Affiliate network, listing
Affiliate sites; describe institutional procedures for processing
Affiliate data and auditing Affiliate charts; describe communications
systems between the Institution and its Affiliates.

b.  Budget

Main members perform two specific activities - they contribute
scientific expertise to the Group, and they accrue patients to Group
clinical trials. Institutional budgets should request those costs
necessary for conduct of Group studies at the institution and for
attendance of a reasonable number of investigators at regular Group
meetings.  The budget of a typical primary member institution should be
devoted largely to personnel, although some variation from this norm is
permissible.  Each institution must develop its request based upon its
unique requirements.  The importance of meticulous justification for
all budget items should be apparent.  The Group Chairperson should
provide each institution with guidance in the preparation of a
reasonable request, in the development of a consistent format for
budget presentation, and in the use of consistent formulas for
institutional travel budgets.

The following budget guidelines apply specifically to Main member
institution applications; the categories refer to the items entitled
"Detailed Budget for Initial Budget Period" on (Form Page 4) of the PHS
398 grant application kit.

1)  Personnel- Precise justification for the percent effort requested
for each position is essential.

a)  Data Management - research costs include the time and effort
involved in accurate data collection and submission.

b)  Other consultant costs (e.g., pathology, radiology),

c)  Intellectual - research costs include the time and effort involved
in developing the research agenda and repertoire of protocols for the
Group, and preparing the results of the Group's research for
publication.

d)  Laboratory investigations - the time and effort related to
additional laboratory investigations specific to the research goals of
the project, i.e., not associated with conventional patient care (note:
most Cooperative Groups place these activities in the Group
Headquarters/Operations Office application.)

e)  Administrative - research costs include the time and effort
involved in coordinating research activities at the institution,
compliance with regulatory activities, quality assurance and study
monitoring procedures and participation in the Group on-site audit
program.

2)  Consultant Costs- These are not usually appropriate in a primary
member institution's budget.  Requests should be justified in detail.
These costs include travel, per diem and consultant fees, if applicable
and within institutional policy.

3)  Supplies/Equipment/Other - research costs include those associated
with communication with the Group office and with Affiliate
institutions, the costs of compiling and mailing data and the costs of
mailing or handling patient-related specimens, forms, and materials
(e.g., slides, X-ray films). Significant equipment costs are unusual;
all must be carefully justified.  The amount of funds requested should
be based on the percent of usage.

4)  Travel - Travel for a reasonable number of the institution's
participating investigators, data managers and nurses to attend the
regular Group meetings should be included in the institutional budgets.
Attendance of investigators at meetings on behalf of the Group, or at
special (i.e., non-routine) meetings of committees of the Group should
generally be funded through the headquarters or statistical office
award, rather than the institution award.

5)  Consortium/Contractual Costs - Separate budget pages with detailed
justification of all requested items should be submitted for each
consortium agreement.  Include applicable indirect costs.

Reimbursement for affiliates accrual will be based on formulas that
must relate to the institution's membership category, scientific and
leadership contributions, and prior performance including accrual and
assessment of data accuracy and timeliness.  A description of how the
formula was determined, including a line item budget breakdown of the
research costs, must be included in the application.  In addition, the
application must include a plan for disbursement of funds that includes
consideration of performance and quality factors including eligibility
and evaluability rates; data accuracy and completeness; and quality of
on-site audits, etc.  The funds received by Affiliates for patient
accrual should be subject to modification based on results of the
Group's performance reviews.

Consortium arrangements and all other contractual arrangements,
including all mechanisms for reimbursement for patient accrual, must be
formalized in writing in accordance with applicable Public Health
Service policy requirements (PHS Grants Policy Statement, revised 9/94,
page 8-17).  A statement that the applicant organization and the
collaborating organization have established or are prepared to
establish a formalized agreement that will ensure compliance with all
pertinent Federal regulations and policies must be included in the
application.  Also include all pertinent biographical sketches and a
list of all other support for all relevant consortium participants.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by DRG and
for responsiveness by the NCI.  Incomplete and non-responsive
applications will be returned to the applicant without further
consideration.

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NCI in accordance with the review criteria
stated below.

The initial peer review may be preceded by a site visit to the Group's
statistical and data management facilities.  The Scientific Review
Administrator is responsible for all aspects of the peer review
process, and will negotiate with the Group chairperson the date,
duration and content of the site visit.  The findings of the site visit
team are provided to the parent review committee during its
consideration of the application.

Because of their interrelatedness, all applications from all components
of a particular Group are reviewed simultaneously.  The content of the
Headquarters/Operations Office application is first evaluated; this
review is an integral part of the review of each individual application
of the Group, regardless of component.  If the initial review committee
recommends the Headquarters application for further consideration, the
committee then assigns a priority score representing the overall peer
review evaluation of the Group and recommends a period of award
(generally three to five years).  If the Headquarters application is
scored, the committee evaluates the applications of the other
individual components.  The committee also develops budgetary
recommendations for each scored application.  If the Headquarters
application is not recommended for further consideration (NRFC), the
applications of the individual components are not reviewed and the
application cannot be funded.

Review Criteria

The review criteria employed by the site visit team and the initial
peer review committee for each of the three operational components are
summarized below:

A.  Group Headquarters/Operations Office

o  Merit of Specific Research Plans  - How meritorious are the research
plans and strategies for each of the major areas of study?  Are they
appropriate in the context of national priorities?  Are guidelines for
the inclusion of women and minorities as research subjects being
followed?  Are there strategies outlined to increase accrual of women
and minorities to clinical trials?

o  Key Personnel - Does the research experience and qualifications of
the Principal Investigator demonstrate understanding of design,
administration, and analysis of multi-institutional clinical trials in
breast and bowel cancer and relevant laboratory studies?

o  Research Methodology - How well designed are the Group's planned
clinical trials?  Will their design allow clinically important
conclusions to be drawn?

o  Patient Accrual - Is the membership of the Group adequate to mount
multiple, concurrent, large-scale clinical trials in breast and bowel
cancer?

o  Efficiency of Study Development - Will the process of study
development proceed in an efficient and timely manner?  Do mechanisms
exist to ensure the rapid development and implementation of important
studies?

o  Timeliness of Study Completion - Will the Group be able to carry out
its planned studies in a reasonable period of time?  Will Intergroup
collaboration be utilized when necessary to satisfy the requirements
for timely completion?

o  Overall Group Priorities - Are the overall priorities of the Group
appropriate?  Are its resources well directed?

o  Developmental Fund Plans - Are the specific plans for the
developmental fund appropriate and consistent with the Group's overall
goals and priorities? Will the fund be well managed with appropriate
oversight?

o  Group Structure and Administration - Will the Group be well
administered by the Chairperson and the Headquarters staff?   Does its
organization and infrastructure allow it to meet its major objectives
and goals?

o  Publication Record - Has the Group developed plans that will
encourage and permit timely publication of  research in quality peer
reviewed journals?

o  Group Cohesiveness - Will the Group function as a cohesive research
team?

o  Interdisciplinary Coordination -   Will there be adequate
interdisciplinary participation in protocol development and design?  Do
protocol investigators reflect the modalities utilized?

o  Membership - Are the criteria for initial and continuing membership
adequate?  Does the Group's periodic evaluations of its members
emphasize both high quality record-keeping and adequate patient
accrual?

o  Companion Research - While not required, Group involvement in
epidemiologic, diagnostic, cancer control, quality of life, cost-
effectiveness, and prevention research, especially as it relates to or
follows logically from the Group's prime therapeutic mission, is a
strength.

o  Patient Advocate Participation - Are there defined plans and roles
for patient advocates in the Group?  Have they been included in the
budget to attend Group meetings?

o  Translational Research  - Is there a well defined and funded plan to
develop a tumor banking system which facilitates correlative studies
into the overall research effort?  While not required, the capacity and
expertise within the Group to develop innovative research ideas based
on laboratory models and pilot these in limited institution trials with
an eye to their potential use as experimental arms in phase III trials
is a strength.

o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

o  Facilities - Are the offices, computer support systems, and overall
parent facility commitment adequate to ensure a smoothly functioning
Headquarters/Operations Office?  Are there any problems with the
structural layout that might serve as an impediment to a focused and
well coordinated Operations Office?

o  Staff - Are the roles of the Headquarter's staff adequately defined
to accomplish the goals of the Group?  Is there an adequately defined
staff to cover the multiple tasks which are the responsibility of the
Operations Office.

o  Budget - Have costs for travel, office supplies, equipment and data
management been adequately justified?  Are detailed costs of Affiliate
members provided?  Are budgetary plans submitted for Group meetings and
consultant fees?

B.  Statistical and Data Management Office

This portion of the evaluation involves three facets: 1) the
performance and capabilities of the statistical and data management
office;  2) the Group's integration of the statistical and data
management office's roles and responsibilities into the overall
research program; and 3) the development and operation of a rigorous
quality control program with on-site auditing.

o  Collaboration in Research - Will there be adequate statistical and
data management collaboration in the development and conduct of the
Group's research?

o  Adequacy of Study Design - Is there evidence that the protocols will
be properly designed statistically?  Will the sample sizes be adequate
to detect realistic and medically important differences?  Will the
assumptions be adequately justified?  Is the expected accrual rate
carefully estimated?  Are the designs used appropriate for the study
questions?  Are endpoint selections and sequential monitoring plans
adequately described and justified?

o  Data Management - Are data management procedures adequate,
appropriate, and consistent with accepted standards?  Are procedures
for the verification of data accuracy adequate? Is there clinical
review of study data?  Do quality assurance and quality control
programs exist, including on-site audits that assure high-quality
research and patient safety?

o  Statistical Analyses -  Are analytical techniques, procedures, and
policies adequate, appropriate, and consistent with accepted standards?
Is there evidence that past publications of the Group Leadership
demonstrate thorough and state-of-the-art methodology, awareness of
problems of multiple analyses, and sufficient independence and lack of
bias of statistical collaborators?

o  Key Personnel - Does the research experience and qualifications of
the Principal Investigator demonstrate understanding of design,
administration, and analysis of multi-institutional clinical trials in
breast and bowel cancer and relevant laboratory studies?

o  Independent Research - While not required, involvement in research
related to the design, conduct and analysis of cancer clinical trials
is a strength.

o  Computing resources - Are computing resources adequate and
appropriate to support Group activities as needed?

o  Facilities - Are the offices, computer hardware, and overall parent
facility commitment adequate to assure smooth and efficient function?
Are there deficiencies in the structural layout which might serve as an
impediment to coordination of Group research efforts?

o  Staff - Are the roles of the staff adequately defined to accomplish
the goals and meet the responsibilities?  Is there an adequate number
of personnel to meet the assigned tasks?

o  Budget - Have costs for the on-site audit plan been accurately
detailed? Is there sufficient funding allotted to carry-out the
multiple quality control tasks required?

C.  Main Members

Both scientific and administrative contributions to the Group, and
patient accrual and data quality enter into this evaluation.

o  Contributions to Group Science - What will be the contributions of
the institution's investigators to the Group's research strategies and
plans? Will the investigators chair research committees and studies?

o  Key Personnel - Does the research experience and qualifications of
the Principal Investigator demonstrate understanding of design,
administration, and analysis of multi-institutional clinical trials in
breast and bowel cancer and relevant laboratory studies?

o  Participation in Group Activities and Administration - How will the
institution's investigators participate in Group activities and
meetings?

o  Interdisciplinary Coordination - To the extent required by the
Group's research, is there adequate interdisciplinary cooperation and
coordination?

o  Patient Accrual - Is the record of patient accrual appropriate in
the context of Main Member/Affiliate accrual goals? Are projections for
the future reasonable and adequate?  Are women and minorities
appropriately included as research subjects on Group trials?  Are there
strategies to increase accrual of women and minorities to clinical
trials?

o  Data Quality - Is the recent data complete, accurate, and submitted
in a timely fashion?

o  Protocol Compliance -  What is the recent record of the quality of
protocol participation?

o  Data Management - Are the institution's data management practices
and procedures adequate and appropriate?

o  Publication - How will the institution's investigators contribute to
publication of Group studies?

o  Translational Research - Although not required, the ability to
conduct phase I and II pilot trials which can then serve to foster the
Group's research goals is a strength.

o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

o  Facilities - Are the treatment facilities adequate to carry out
clinical research?  Does each Affiliate have a well organized central
site which will coordinate the activities of its members?

o  Staff - Are there adequate data managers and nursing support to meet
the patient care and data submission needs of clinical trials?  Is the
relationship between Affiliate and their Main Members carefully
explained, including the responsibilities of the P.I. at each
institution?

o  Budget - Have costs for on-site auditing of Affiliates been included
(if this is the mechanism chosen by the Group for auditing of
Affiliates)?  Are travel and equipment costs adequately detailed?  Is
there adequate justification of personnel costs?

AWARD CRITERIA

Applications recommended by the National Cancer Advisory Board will be
considered for award based upon (a) technical merit of the application
as reflected in the priority score (b) availability of resources, and
study population and (c) availability of funds.  Furthermore, the
applicant organization must indicate a commitment to accept provisions
outlined under the SPECIAL REQUIREMENTS section, Terms and Conditions
of Award.  The anticipated date of award is March 1, 1996.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding scientific and/or administrative issues to:

Richard S. Ungerleider, M.D.
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 741
6130 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (if using express mail)
Telephone:  (301) 496-6056 or (301) 496-2522
FAX:  (301) 402-0557
Email:  ungerler@dct.nci.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (if using express mail)
Telephone:  (301) 496-7800, ext. 282
FAX:  (301) 496-8601
Email:  WOLFREYC@GAB.NCI.NIH.GOV

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.395, Cancer Treatment Research.  Awards are made under
authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants policies and Federal Regulations
42 CFR 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routing education, library,
day care, health care or early childhood development services are
provided to children.  This is consistent with the phs mission to
protect and advance the physical and mental health of the american
people.

.

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