Full Text CA-97-002
 
CONSORTIUM THERAPEUTIC STUDIES OF PRIMARY CENTRAL NERVOUS SYSTEM
MALIGNANCIES IN ADULTS
 
NIH GUIDE, Volume 25, Number 40, November 22, 1996 (see reissuance
RFA-CA-04-001)
 
RFA:  CA-97-002
 
P.T. 34

Keywords: 
  Nervous System 
  Cancer/Carcinogenesis 
  Chemotherapeutic Agents 

 
National Cancer Institute
 
Letter of Intent Receipt Date:  January 24, 1997
Application Receipt Date:  March 13, 1997
 
PURPOSE
 
The Cancer Therapy Evaluation Program (CTEP) and the Radiation
Research Program (RRP) of the Division of Cancer Treatment Diagnosis
and Centers (DCTDC) at the National Cancer Institute (NCI) invite
applications for cooperative agreements (U01) from consortia of
institutions to perform Phase I and II clinical evaluations of
promising new therapeutic agents or approaches for the treatment of
primary central nervous system (CNS) malignancies in adult patients,
especially glioblastoma multiform and other high grade gliomas, and
to perform ancillary laboratory studies of aspects of CNS tumor
biology with potential clinical implications.  The NCI is seeking
talented scientists from academic, non-profit and for-profit research
organizations who will interact with other members of the consortium,
and with NCI in a concerted way to conceive, create, and evaluate new
approaches to the therapy of CNS tumors. Integrated packages of
individual applications are encouraged, with the lead institution of
a proposed consortium indicating which participating institutions
will provide organizational support, scientific leadership,
laboratory capabilities, and/or patient resources.  Each consortium
of institutions will be referred to as a CNS Consortium (CNSC) for
the purpose of this RFA.  The purpose of the proposed awards is to
stimulate cooperative efforts to improve treatment and to develop
more effective therapies for brain tumors.
 
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 RFA,
Consortium Therapeutic Studies of Primary Central Nervous System
Malignancies in Adults, 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 202/512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by North American non-profit and
for-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Applications from minority individuals, women, and persons with
disabilities are encouraged.
 
It is essential that applications be submitted as an integrated
package from a team or consortium (CNSC) of medical institutions (a
minimum of five Participant Member Institutions that agree to work
together with a single Project Leader and a single administrative
structure, and submit applications that will be reviewed in relation
to the consortium.  Eligible institutions may apply for any or all of
the following types of award: (1) Participant Member Institution; (2)
Central Operations Office/Coordinating Center; (3) Pharmacokinetics
Laboratory.  Participant Member Institution and Central Operations
Office/Coordinating Center applications must be submitted separately,
but the pharmacokinetics lab activity may be submitted separately or
be combined with either of the other types in a single application.
Together, the institutions in the consortium would encompass
experience in investigational drug clinical trials, access to
sufficient numbers of primary CNS tumor (glioma) patients to enter 60
to 80 fully evaluable cases per year and complete three to four Phase
I and II protocols, expertise in laboratory investigation of the
biology of human gliomas, and access to a Central Operations Office
for coordination of research activities and data analysis.
Ordinarily, the Central Operations Office/Coordinating Center would
be expected to reside at the Project Leader's institution.  Detailed
requirements are listed below in Terms and Conditions of Award,
Awardee Rights and Responsibilities.
 
MECHANISM OF SUPPORT
 
The administrative and funding instrument to be used for this program
will be a cooperative agreement (U01), an "assistance" mechanism, in
which substantial NCI scientific and/or programmatic collaboration
with the awardee is anticipated during performance of the activity.
Under the cooperative agreement, the NCI purpose is to support and/or
stimulate the recipient's activity by working jointly with the award
recipient in a partner role, but is not to assume direction, prime
responsibility, or a dominant role in the activity.  Details of the
responsibilities, relationships, and governance of the study to be
funded under cooperative agreements(s) are discussed later in this
document under the section "Terms and Conditions of Award".
 
Awards and level of support depend on receipt of a sufficient number
of applications of high scientific merit. 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.  The total project period for each application submitted in
response to the RFA may not exceed five years.  The earliest
anticipated award date is December 1, 1997. At this time, the NCI has
not determined whether or how this solicitation will be continued
beyond the present RFA.
 
FUNDS AVAILABLE
 
Approximately $2,200,000 in total costs per year for five years will
be committed to specifically fund applications submitted in response
to this RFA.  It is anticipated that new and/or competing
continuation awards will be made to between five and eight individual
members of each of two consortia, although larger consortia will be
considered with justification.  Because of the variation in numbers
of patients to be accrued and the type of award, it is anticipated
that the size of Participant Member Institution awards will vary.  It
is anticipated that the Central Operations Office/Coordinating Center
will require approximately $250,000-$300,000 direct costs per year
(of which $100,000 is reserved for a Discretionary Fund for
laboratory studies and the shipping of patient specimens).
 
RESEARCH OBJECTIVES
 
A.  Background
 
Primary malignant brain tumors occur in approximately 18,000 adults
annually in the US and have been increasing in incidence, especially
in the elderly.  Meaningful therapeutic improvement has been made for
the less common histologic types such as ependymomas,
oligodendrogliomas, and CNS lymphomas.  However, for the largest
category, astrocytomas of various grades, little progress has been
made. Aggressive multimodality therapy has been shown to improve
short term survival by two- to three-fold, but average survival for
patients with high-grade gliomas is only 9-15 months and, despite the
fact that these cancers rarely metastasize, they remain essentially
100 percent lethal.
 
Limited therapeutic success is related to many factors, including the
unique biology of high grade gliomas and the susceptibility of
adjacent normal brain to adverse effects of treatment.  There has
also been an extremely limited number of identified agents with
therapeutic activity, which may well be due to inherent resistance to
the classes of agents that have been available.  However, in part, it
may also reflect the fact that relatively few compounds have received
thorough clinical evaluation. In addition, clinical trials have been
hampered by the fact that tumor status, the adverse sequelae of
therapy, and the effects of ancillary treatments (such as steroids)
are very challenging to segregate when assessed either by clinical
examination or conventional diagnostic imaging.  Optimal response
evaluation and management of these patients continues to require
complex and well coordinated interdisciplinary management involving
neurosurgeons, neurologists, medical and radiation oncologists,
neuroradiologists, and neuropathologists, so that relatively few
programs have been optimally suited to undertake such trials.
 
Clinical investigations of new strategies  to treat such tumors are
needed.  Collaborative interactions between clinicians and laboratory
scientists and between clinicians and diagnostic imagers are
essential features of these investigations.  The special skills of
experienced tumor neurosurgeons, neuro-oncologists, radiation
therapists, and neuroradiologists with access to the latest
generation of imaging equipment will be required.  NCI is therefore
seeking multidisciplinary and multi institutional teams of talented
scientists from non-profit and for-profit research organizations who
will interact with CTEP and RRP in a concerted way to conceive,
create, and evaluate new approaches to therapy of CNS malignancies.
Scientific approaches should be broad and reflect the creativity and
capabilities of team participants, including surgical, medical,
radiotherapeutic, diagnostic imaging, laboratory and statistical
skills.
 
New clinical research opportunities exist with the development of
novel cytotoxic drugs, drug resistance inhibitors, radiation
enhancers, radiosurgery techniques, antiangiogenic agents, signal
transduction inhibitors, antisense oligonucleotides, differentiating
agents, immune modulators, antibody-based approaches, regional
delivery techniques, and new approaches to gene therapy.  Team
objectives and approaches will be investigator-originated but
consistent with program aims of improving the survival and quality of
life for persons with primary CNS malignancies and providing
fundamental insights into the biology of these tumors.
 
B.  Definitions
 
COOPERATIVE AGREEMENT - An assistance mechanism in which substantial
NCI programmatic  involvement with the recipient is anticipated
during performance of the planned activity.
 
CENTRAL NERVOUS SYSTEM CONSORTIUM (CNSC) - The consortium of
institutions (minimum of five members) who are submitting research
grant applications together to conduct Phase I/II clinical trials and
ancillary laboratory studies.  Each CNSC also contains an application
for a Central Operations Office/Coordinating Center.  Each consortium
will consist of talented and experienced individuals in multiple
disciplines (e.g. medical oncology, neurosurgery, neurology,
radiotherapy, radiobiology, pharmacology, molecular biology,
pathology, biostatistics).
 
CENTRAL OPERATIONS OFFICE/COORDINATING CENTER - An administrative
unit that coordinates all CNSC activities. Responsibilities include
administrative management, coordination of protocol development and
submission, study conduct, quality control and protocol performance
monitoring, statistical analyses, adherence to requirements regarding
NCI drug accountability and FDA, OPRR and HHS regulations, and
protocol and institutional performance reporting.  Statistical
responsibilities include experimental design, participation in study
planning and coordination, collection and analysis of patient and
laboratory data, data management and analysis, data monitoring, and
reporting of data. The Central Operations Office/Coordinating Center
may consist of a consortium with the statistics center located at
another institution.
 
PROJECT LEADER -  The person who submits the application for the
Central Operations Office/Coordinating Center and who is responsible
for the CNSC as a whole.  The consortium of Participant Member
Institutions must agree to work together with the Project Leader.
The Project Leader is responsible for coordinating the CNSC
activities scientifically and administratively.  The Project Leader
may also be the principal investigator on a Participant Member
Institution application.
 
PARTICIPANT MEMBER INSTITUTION - The individual research grant
application from an institution who is participating in the CNSC. The
Participant Member Institution may conduct clinical trials and/or
laboratory studies.
 
PRINCIPAL INVESTIGATOR - The person who submits the single
application for the Participant Member Institution and who is
responsible for performance of the key personnel of that application.
The Principal Investigator (PI) provides the scientific leadership
for the Participant Member Institution.
 
NCI PROGRAM DIRECTOR - The CTEP extramural grants staff member (cited
in the INQUIRIES SECTION) who will coordinate DCTDC interactions and
provide guidance for the overall program within the NCI. He/she is
available for consultation during preparation of applications, as
well as throughout the course of the research conducted under these
cooperative agreements.  He/she also serves in a back-up role for the
NCI Scientific Coordinator.
 
NCI SCIENTIFIC COORDINATOR - The Senior Investigator, Clinical
Investigations Branch, CTEP, DCTDC, NCI, who interacts scientifically
with the Applicant/Awardee Institutions.
 
STEERING COMMITTEE - Each consortium's steering committee will be
composed of the Project Leader, PIs, the NCI Scientific Coordinator,
and the NCI Program Director, and will be the main oversight body of
the consortium.
 
DISCRETIONARY FUND - A fixed portion ($100,000) of the award to the
Central Operations Office/Coordinating Center that will be allocated
according to the instructions of the Steering Committee.  Appropriate
uses may include seed funding for laboratory projects, shipment of
samples, supplementation of existing budgets for patient accrual or
special clinical costs, auditing of clinical trials, or other
purposes.
 
C.  RESEARCH GOALS AND SCOPE
 
The primary goal of this initiative is to stimulate clinical research
in the treatment of primary CNS malignancies in adult patients by
providing support for consortia of institutions to take advantage of
promising new developments and perform Phase I and II clinical
evaluations of innovative approaches or agents.  A secondary goal is
to utilize the consortia as a mechanism for sharing human brain tumor
specimens among investigators conducting laboratory studies relevant
to the biology, clinical behavior, or therapy of CNS tumors,
particularly malignant gliomas.
 
Each CNSC will be formed for the purpose of:  (1) sharing expertise
of researchers in multiple disciplines; (2) conducting joint phase I
and II clinical trials to provide adequate patient populations and
timely completion; and (3) sharing of tumor specimens and data useful
in the conduct of clinical pharmacologic and correlative laboratory
studies. Participant Member Institutions in the proposed consortium
may be involved in clinical trials and/or laboratory studies.
 
It is anticipated that two consortia will be established, comprising
a total of 10-16 institutions.  Each CNSC will select the specific
agents to be tested in accord with their scientific interest and
expertise and will develop a series of appropriate Phase I or Phase
II trials with supporting protocol documents.  Each applicant CNSC
should submit as examples one or more draft clinical protocols as
supplements to the Central Operations Office/Coordinating Center
(Project Leader) and the Participant Member Institution applications.
 
Each CNSC must be able to document access to adequate numbers of
patients with CNS tumors and a history of accrual of patients to
clinical trials adequate  to support three-four phase I or II trials
(60-80+ patients) per year.  In addition, proposed consortia must
have: (1) adequate radiotherapy support for clinical trials utilizing
radiation in combination with other modalities; (2) adequate central
data collection and processing capabilities as well as biostatistical
expertise; (3) adequate pathology support for both institutional
tumor classification and central neuropathology review and for
banking and distribution of tumor tissues for concurrent and future
laboratory studies; (4) mechanisms to collect and store patient
specimens for laboratory studies being conducted by institutions in
the CNSC; (5) expertise in antineoplastic drug
pharmacology/pharmacokinetics.
 
Each CNSC, with the assistance of the NCI Scientific Coordinator and
Program Director, will develop a plan for prioritization of
investigational trials.  The NCI will provide assistance in design of
trials and may provide NCI-sponsored IND agents or provide assistance
to the awardee(s) by sponsoring or cross-referencing INDs for
selected agents.  A CNSC may also carry out some of its trials with
agents that are not sponsored by NCI.
 
The correlative laboratory research program in a CNSC should have
demonstrable capability to address at least one field of research
into the biology of human malignant gliomas with some potential for
future clinical relevance.  Examples of research fields for
laboratory studies include:  molecular genetics and cytogenetics,
gene function and expression, signal transduction pathways,
radiobiology, growth regulation, metabolism, differentiation and gene
modulation by investigational agents, intracellular metabolism,
mechanisms of drug resistance in tumor cells, CNS pharmacokinetics,
invasion and spread, cytokine production or interactions, immune
function and antigen expression, or other aspects that may have
clinical implications or lead to new therapeutic approaches.
 
It is not expected that funding for these clinical consortia will be
adequate to support to completion high quality laboratory projects
(other than pharmacokinetic projects directly linked to the clinical
protocols).  Some funding for lab pilot studies will be available
through the CNSC Discretionary Fund.  However, the expectation is
that investigators from within the consortium membership will have in
place or will seek other funding for laboratory projects that can
draw upon and utilize the substantial tissue and clinical data
resources of the CNSCs.  The intent is that each CNSC should
establish under these cooperative agreements an infrastructure that
will promote this type of interaction.
 
Correlative laboratory studies need not be directly related to
individual clinical Phase I/II trials but should attempt to utilize
the large clinical database that will be generated by the consortium
to identify potential correlates of tumor behavior.  Laboratory
studies should naturally be based on strong and testable hypotheses.
Within the CNSC package of applications, there should be an initial
plan for developing one or more laboratory programs that can utilize
the resources provided by the CNSCs clinical trials.  A clear
rationale should be given for the experimental design and
technological methodologies selected.  Preliminary data from
appropriate tumor models or analysis of patient specimens should be
provided to support the feasibility of each study.  The laboratory
assays must utilize tumor specimens from patients and there should be
an established plan for prioritization of specimen distribution to
collaborating laboratories.
 
Participating institutions primarily involved in laboratory studies
may accrue patients on CNSC clinical trials if the minimum clinical
resources are in place (See Eligibility Requirements).
 
The cooperative approach outlined in this RFA allows for interactions
among successful applicants, with the assistance of NCI extramural
staff, to perform Phase I and Phase II trials of therapeutic
approaches and ancillary laboratory studies.  This mechanism retains
the decision-making prerogatives of the Principal Investigator and
his/her colleagues, but at the same time, permits the active
participation of NCI in research activities.  (See Terms and
Conditions of Award)
 
SPECIAL REQUIREMENTS
 
A.  Terms and Conditions of Award
 
The administrative and funding instrument used for this program is a
cooperative agreement (U01), an "assistance" 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 staff.  The role of the NCI staff as described throughout these
terms and conditions of award is to facilitate and assist 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 NCI staff listed below has very specific and well defined
responsibilities in terms of investigational agent development and
the role of DCTDC as a drug sponsor as defined in CFR 21 part 312.
 
These Terms and Conditions of Award are in addition to and not in
lieu of otherwise applicable OMB administrative guidelines, HHS grant
administration regulations at 45 CFR Part 74, and other HHS, PHS and
NIH grant administration policy statements.
 
Awardee Rights and Responsibilities
 
It is the responsibility of the CNSC to develop the details of the
clinical and laboratory research design, including definition of
objectives and approaches, planning, implementation, analysis, and
publication of results, interpretations and conclusions of studies.
The CNSC shall, with CTEP assistance, develop Phase I and II
protocols for clinical cancer research in accord with the research
interests, abilities and goals of the CNSC, and submit them to CTEP
for review as appropriate prior to their implementation.
 
1.  Protocol Development
 
It is anticipated that decisions in all CNSC activities will be
reached by consensus of the collaborating member institutions under
the leadership of the CNSC Project Leader.  The Project Leader shall
designate a Protocol Chairperson for each proposed study.  The
Project Leader along with coordinating Central Operations
Office/Coordinating Center staff will be responsible for
communication with the appropriate CTEP staff.
 
2.  The CNSC Central Operations Office/Coordinating Center
 
The CNSC Central Operations Office/Coordinating Center, under the
leadership of the Project Leader 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 CNSC funded activities and
made by the CNSC institutions or affiliates will be coordinated by
the Project Leader with the assistance of the CNSC Central Operations
Office/Coordinating Center.
 
3.  Protocol Submission
 
The CNSC Central Operations Office/Coordinating Center, under the
leadership of the Project Leader, will submit CNSC protocols to the
CTEP Protocol and Information Office in a timely fashion for review
and approval by NCI.  It is recommended that protocols involving NCI
sponsored agents be preceded by a written Letter of Intent (LOI) from
the CNSC to the CTEP LOI Coordinator declaring interest in conducting
a particular study. The LOI shall describe the hypothesis to be
investigated, the general design of the contemplated trial plus
relevant information on accrual capabilities to document feasibility.
Protocols will be developed and submitted and studies will be
conducted in accordance with the DCTDC "Investigator's Handbook"
(available upon request from the Program Director at the address
below).  The Project Leader, with the assistance of the Central
Operations Office/Coordinating Center staff, will communicate the
results of the NCI review of protocols to the CNSC Participant Member
Institutions.
 
4.  Prioritization of Studies
 
The CNSC Project Leader and the Principal Investigators of the
Participant Member Institutions will develop, together with the NCI
Scientific Coordinator and Program Director, mutually acceptable
plans for prioritization of clinical protocols, laboratory studies,
and distribution of clinical specimens and tissues.
 
5.  Quality Control
 
The CNSC will establish mechanisms for quality control of therapeutic
and diagnostic modalities employed in its trials. Quality control at
a minimum must consist of:
 
a) 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.
 
b) Radiation Therapy:  Review (either concurrent or retrospective) of
port films and compliance with protocol- specified doses for
individual patients, where relevant. Determination of adequacy of
radiation delivery with the assistance of the Radiological Physics
Center (RPC), whose functions usually include equipment dosimetry,
periodic institutional visits and other aspects of physics review.
 
c) Chemotherapy:  Review of flow sheets with determination of
protocol compliance in dose administration and dosage modification.
 
d) Neurosurgery:  Assessment of adequacy of protocol-specified
surgical procedures (where relevant) through review of operative
notes and study-specific surgical forms.
 
e) Diagnostic Imaging:  Central review of claimed responses and
adequacy of imaging.
 
6.  Study Monitoring
 
The CNSC will establish mechanisms for study monitoring. The CNSC is
responsible for assuring accurate and timely knowledge of the
progress of each study through:
 
a) establishing procedures for assigning dose level at the time a new
patient is entered, and assuring that the required observation period
has elapsed before beginning a higher dose level;
 
b) registration, tracking and reporting of patient accrual and
adherence to defined accrual goals; appropriate attempts to accrue
patients who fulfill NIH Guidelines for accrual of women and
minorities to clinical trials with appropriate documentation and
reporting of accrual as specified by NIH Guidelines;
 
c) ongoing assessment of case eligibility and evaluability;
 
d) timely medical review and assessment of patient data;
 
e) rapid reporting of treatment-related morbidity (adverse drug
reactions) and measures to ensure communication of this information
to all parties;
 
e) interim evaluation and consideration of measures of outcome, as
consistent with patient safety and good clinical trials practice;
 
g) timely communication of results of studies;
 
7.  Data Management and Analysis
 
The CNSC will develop procedures to ensure that data collection and
management are:  (1) adequate for quality control and analysis; (2)
as simple as appropriate in order to encourage maximum participation
of physicians entering patients and to avoid unnecessary expense; and
(3) coordinated across the participating institutions.
 
8.  Investigational Drug Management
 
Investigators performing trials under cooperative agreements
involving DCTDC Investigational Agents must be NCI registered
investigators (form 1572) and will be expected to implement CTEP
requirements described in the DCTDC Investigators' Handbook for
storage and accounting for investigational agents, to abide by
NCI/HHS Drug Accountability Records (DAR) procedures, and to comply
with all FDA requirements for investigational agents.
 
9.  CNSC Compliance with Federally Mandated Regulatory Requirements
 
The CNSC is responsible for establishing procedures for all
participating institutions to comply with FDA regulations for studies
involving investigational agents and OPRR requirements for the
protection of human subjects.  These procedures are:
 
a) methods for assuring that each institution where investigators are
conducting CNSC trials has a current, approved assurance on file with
the OPRR; that each protocol is reviewed and approved by the
responsible Institutional Review Board (IRB) prior to patient entry;
that each protocol is reviewed at least annually by the IRB so long
as the protocol is active; that each investigator is registered with
the Drug Management and Authorization Section (DMAS), CTEP, with a
current 1572 form on file; and that each patient (or legal
representative) gives written informed consent prior to entry on
study.
 
b) a system for assuring timely reporting of all serious and
unexpected toxicities to the Investigational Drug Branch (IDB), CTEP
according to CTEP guidelines (mailed annually to all registered
investigators). This requires reporting Adverse Event Reactions
(AERs) by telephone to the IDB Drug Monitor within 24 hours of the
event and requires a written report to follow within 10 working days.
 
c) a system for ensuring that the data required for the conduct and
auditing of clinical trials with DCTDC-sponsored investigational
agents (see DCTDC Investigator's Handbook) is provided to the
Clinical Trials Monitoring Service, an NCI contractor.
 
10.  Progress Review
 
The CNSC will establish a mechanism for assessing performance of its
members, with particular attention to accrual of adequate number of
eligible patients onto consortium trials, timely submission of
required data, conscientious observance of protocol requirements,
authorship and participation in group leadership. This mechanism will
include a procedure for recommending an adjustment of institutional
funds within the consortium as appropriate for the level of
participation in consortium activities, including (but not limited
to) accrual.
 
11.  Attendance at Meetings
 
The CNSC Project Leader and appropriate representative(s) of the CNSC
participating member institutions , shall meet twice a year with the
NCI Scientific Coordinator and Program Director to review CNSC
progress, establish priorities, and plan future activities.
Additional meetings between the NCI staff and the Project Leader will
be held if necessary.
 
12.  Reporting Requirements
 
Reporting requirements will be in agreement with FDA regulations and
NCI procedures.  Annual progress reports will be submitted to the NCI
and will include at a minimum summary data on protocol performance by
the awardee and each participating institution. In addition, data
summary reports will be requested prior to the due date of the annual
report to the FDA required of IND sponsors.  A system for providing
such information in a timely manner must be in place.
 
13.  Publication of Data
 
Timely publication of major findings is encouraged. Publication or
oral presentation of work done under this agreement will require
appropriate acknowledgment of NCI support.  The NCI will have access
to all data generated under this cooperative agreement and may
periodically review the data.  The awardee will retain custody and
primary rights to the data consistent with current HHS, PHS and NIH
policies.
 
NCI Staff Responsibilities
 
It is expected that the dominant role and prime responsibility for
the activity will reside 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
Director and NCI Scientific Coordinator.  The NCI Program Director
and Scientific Coordinator will be the main contact points for all
facets of the scientific interaction with the awardees.  Two NCI
staff are required for the coordination of activities, to expedite
progress, and to provide advice to the awardee on specific scientific
and/or analytic issues in addition to programmatic issues.
 
1. CTEP as a Scientific Resource for NCI-supported Phase I and II
Clinical Trials Investigations
 
The NCI Scientific Coordinator will serve as a resource available to
the for scientific information with respect to treatment regimens and
clinical trial design. The NCI Scientific Coordinator will assist the
CNSC as appropriate in developing information concerning the
scientific basis for specific trials and also will be responsible for
advising the CNSC of the nature and results of relevant trials being
carried out nationally or internationally.  The NCI Program Director
and Scientific Coordinator will sponsor an initial strategy meeting
with the awardees to review the research plans proposed to ensure
that they are compatible with the overall goals of the RFA, to ensure
avoidance of duplication of effort, and to ensure the most effective
use of available resources, including investigational agents. The NCI
Scientific Coordinator and Program Director will also sponsor
strategy meetings as needed, to be attended by investigators in the
CNSC and other investigators as appropriate.
 
At these meetings relevant information will be reviewed, national
research goals discussed, and the outstanding research questions
established and prioritized by the CNSC investigators.  The NCI
Scientific Coordinator will also provide updated information on the
efficacy and toxicity of investigational new agents supplied to the
CNSC under an Investigational New Drug (IND) Application sponsored by
the DCTDC.
 
2.  CTEP Assistance in Protocol Development
 
The protocol must be a detailed written plan of a clinical experiment
mutually acceptable to the proposing CNSC and to the CTEP Protocol
Review Committee (PRC).  Communication at the various stages of
protocol development is encouraged as necessary to promote protocol
development and implementation.  It is recommended that protocols
utilizing NCI-sponsored agents be preceded by a written Letter of
Intent (LOI) from the CNSC declaring interest in conducting a
particular study. The PRC will formally review the LOI. Following
review, the NCI Scientific Coordinator will provide a Program
response to the CNSC and will address the following issues:  (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; (c) availability of
investigational agents; (d) the PRC's assessment of the scientific
rationale and value of the proposed study, its design, and
statistical requirements; and (e) the implementation of the study, if
indicated.  The LOI mechanism is designed for preliminary review and
is recommended to expedite protocol development and implementation
and to facilitate agreement on study priority and design (see the
DCTDC Investigator's Handbook, pp 32-35, available on request from
the NCI Program Director at the address below, for further discussion
of these mechanisms).
 
3.  CTEP Review of Proposed Protocols
 
All CNSC protocols, including protocols utilizing agents not
sponsored by NCI, will be reviewed by the PRC, which meets weekly and
is chaired by the Associate Director, CTEP.  Ad hoc reviewers,
external to NCI, will be utilized when deemed appropriate by the PRC
chairperson.  Following the review of the protocol by the PRC, the
NCI Scientific Coordinator will provide the CNSC with a consensus
review that describes recommended modifications and other
suggestions, as appropriate (see the DCTDC Investigator's Handbook,
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 unnecessary duplication with other ongoing studies; (d)
the appropriateness of study design; (e) consistency with development
plans for particular IND agents; (f) a satisfactory projected accrual
rate and follow-up period; (g) patient safety; (h) compliance with
federal regulatory requirements; (i) adequacy of data management; (j)
appropriateness of patient selection, evaluation, assessment of
toxicity, response to therapy and follow-up; and (k) method of
monitoring to be used.
 
If a proposed protocol is disapproved, the specific reasons for lack
of approval will be communicated in writing by the NCI Scientific
Coordinator to the CNSC 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 NCI Scientific Coordinator will be available to
assist the CNSC in developing a mutually acceptable protocol,
consistent with the research interests, abilities and strategic plans
of the CNSC and of the NCI.
 
The CNSC will not expend NCI funds to conduct any study disapproved
by CTEP unless CTEP's disapproval has been modified by the
arbitration process outlined below.
 
4.  CTEP Involvement in Protocol Closure
 
The NCI Program Director and Scientific Coordinator will monitor
protocol progress.  A protocol study may be closed to accrual for
reasons including:  (a) insufficient accrual rate; (b) accrual goal
met; (c) poor protocol performance; (d) patient safety and regulatory
concerns; (e) study results are already conclusive; and (f) emergence
of new information that diminishes the scientific importance of the
study question.  NCI will not provide investigational agents or
permit expenditures of NCI funds for a study after requesting closure
(except for patients already on-study).
 
5.  CTEP involvement in Investigational New Drug Applications
 
a.  The NCI will be willing to consider filing or cross filing an IND
for investigational drugs evaluated in the Phase I and II Clinical
Trials.  This would apply to drugs not developed in the NCI drug
development program.
 
b.  The NCI Program Director assisted by the Chief, Regulatory
Affairs Branch (RAB), CTEP will advise investigators of specific
requirements and changes in requirements concerning IND sponsorship
that the FDA may mandate. Investigators performing trials under
cooperative agreements will be expected, in cooperation with the NCI,
to comply with all FDA monitoring and reporting requirements for
investigational agents.
 
c.  Investigators performing NCI funded Phase I and II Clinical
Trials will be advised by the NCI Scientific Coordinator and Program
Director of potential studies that will be relevant to new avenues of
cancer therapy. When this involves investigational agents, the NCI
Scientific Coordinator assisted by the Chief, RAB, CTEP will advise
the investigators of the specific clinical information that will be
needed from the clinical trials for that information to be acceptable
to the FDA for inclusion in a new drug application (NDA).
 
6.  CTEP Review of Federally Mandated Regulatory Requirements
 
The Chief, Clinical Trials Monitoring Branch (CTMB), through the NCI
Scientific Coordinator, will advise the CNSC regarding mechanisms to
meet FDA regulatory requirements for studies involving
DCTDC-sponsored investigational agents and the Office for Protection
from Research Risks (OPRR) requirements for the protection of human
subjects by the CNSC institutions.  (See AWARDEE RIGHTS AND
RESPONSIBILITIES, above).  For specific Phase I and II trials with
NCI-sponsored investigational agents, the NCI has contracted for a
Clinical Trials Monitoring Service (CTMS) to document regulatory
compliance, to maintain a computerized data base and to produce
periodic routine reports of the results, and special reports as
necessary.
 
7.  Access to Data
 
The NCI will have access to all data generated under this cooperative
agreement and may periodically review the data. Data must also be
available for external monitoring as required by NCI's Drug Master
File Agreement with the FDA relative to the responsibility of the NCI
as an IND agent sponsor.  The awardee will retain custody and primary
rights to the data consistent with current HHS, PHS and NIH policies.
 
8.  CTEP Review of Progress
 
Performance of each CNSC will be reviewed at least annually by the
NCI Program Director and Scientific Coordinator on the basis of the
information provided at the semi-annual and other meetings, in the
annual progress reports and in the data summary reports submitted to
the IDB Drug Monitor or by CTMS reports.  In addition, periodic
accrual information may be requested from the CNSC by the NCI
Scientific Coordinator for all active studies when deemed
appropriate.
 
Insufficient patient accrual or progress, or noncompliance with the
terms of award, including these Terms and Conditions of Award, may
result in a reduction of budget, withholding of support, suspension
or termination of the award.
 
Collaborative Responsibilities
 
1.  Service on the Steering Committee
 
The Steering Committee for each CNSC will be composed of the Project
Leader, Principal Investigators of Participant Member Institutions,
NCI Scientific Coordinator, and the NCI Program Director.  The
Project Leader will serve as Chairperson of the Steering Committee.
He/she is responsible for coordinating the Committee activities, for
preparing meeting agendas, and for scheduling and chairing meetings.
The Steering Committee has primary responsibility to design research
activities, establish priorities, and develop and provide preliminary
approval of protocols (prior to submission to NCI and final NCI
approval).  The Steering Committee will also authorize the spending
of funds from the Discretionary Fund.  Appropriate uses may include
funding for pilot laboratory studies, shipment of specimens, and
supplementing existing budgets for patient accrual and auditing of
clinical trials.  The Steering Committee Chairperson will document
actions taken and progress in written reports to the NCI Program
Director, and will provide periodic supplementary reports to
designated NCI staff upon request.
 
2.  CNSC meetings
 
The NCI Scientific Coordinator and Program Director will attend
semi-annual CNSC meetings with the PIs and Project Leaders to review
relevant scientific information, to review progress in the clinical
trials, and to review the status of newly available investigational
agents in order to plan future activities.
 
3.  The CNSC shall, with CTEP assistance as described in the above
terms for the NCI staff responsibilities, develop Phase I and II
protocols.  The protocols must be mutually acceptable to the CNSC and
the CTEP Protocol Review Committee.
 
4.  The CNSC investigators will be asked to meet periodically with
the NCI Scientific Coordinator and NCI Program Director and with
investigators involved in other NCI sponsored brain tumor clinical
research programs to discuss issues of mutual collaboration and
interest.
 
Arbitration
 
Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), excluding patient safety issues or
regulatory compliance, between award recipients and the NCI may be
brought to arbitration.  An arbitration panel composed of one awardee
nominee, one NCI nominee, and a third member with clinical trials
expertise chosen by the other two nominees will be formed to review
the CTEP decision and recommend an appropriate course of action to
the Director, DCTDC.  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.
 
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 4928 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 have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) 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 are asked to submit, by January 24, 1997, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Project
Leader, 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 subsequent applications, the information
is helpful in planning for the review of applications.  It allows NCI
staff to estimate the potential review workload and to avoid conflict
of interest in the review.
 
The letter of intent is to be sent to:
 
Ms. Diane Bronzert
Division of Cancer Treatment Diagnosis and Centers
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Boulevard MSC 7436
Bethesda, MD  20892-7436
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-8866
FAX:  (301) 480-4663
Email:  BRONZERD@DCT.NCI.NIH.GOV
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for cooperative agreements.  These forms are available at
most institutional offices of sponsored research and may be obtained
from the Office of Extramural Outreach and Information Resources,
NIH, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910,
telephone (301) 435-0714, e-mail: asknih@odrockm1.od.nih.gov.
 
An application from a currently funded grantee will be a competitive
continuation and must include a progress report, which at a minimum
consists of a summary of prior Phase I or II
activities/accomplishments, including a clear presentation of
pharmacokinetic studies, pharmacodynamic correlations and results,
conclusions of correlative laboratory studies and annual accrual over
the funding period.  A summary of accrual by gender and race and/or
ethnicity to all trials conducted during the project period must be
provided.
 
The Central Operations Office/Coordinating Center as lead institution
should submit a research grant application in which they should list
the anticipated Participant Member Institutions, and include proposed
clinical protocols in the Appendix.  (The Central Operations
Office/Coordinating Center application must be a separate document
from any application from a Participant Member Institution; if a
single institution will be applying for both participation in
clinical and/or laboratory studies and as the Central Operations
Office/Coordinating Center, two applications will be necessary.)
Each Participant Member Institution should submit an individual
research grant application and should indicate the Central Operations
Office/Coordinating Center of the CNSC consortium in which they
intend to participate. Participant Member Institutions should
identify the Central Operations Office/Coordinating Center by listing
this institution in parentheses following the title of the grant.
Participant Member Institutions conducting clinical trials should
include copies of the proposed CNSC clinical protocols in the
Appendix.
 
Because the Terms and Conditions of Award discussed above will be
included in all awards issued as a result of this RFA, it is critical
that each applicant include specific plans for responding to these
terms.  Plans must describe how the applicant will comply with staff
involvement.
 
The CNSC and the  members of each proposed Consortium must
demonstrate in the application the ability to meet the following
requirements:
 
A.  Requirements for the Consortium (CNSC) as a whole:
 
1. A commitment to participate in multi-institutional protocols and
documentation of facilities and professional personnel available,
committed, and expert in conducting brain tumor clinical trials.
This includes assignment of appropriate specialist collaborators
including, but not limited to, medical oncologists, radiation
therapists, neurologists, neurosurgeons, neuroradiologists, and
neuropathologists.
 
2. A Central Operations Office/Coordinating Center for biostatistical
support, collection, analysis, reporting, and quality control of data
from Phase I and II trials and related laboratory investigations.
Detailed requirements may be found in RESEARCH OBJECTIVES,
DEFINITIONS above.
 
3. The applicant CNSC and each of its participating clinical
institutions must have adequate central data collection and
processing capabilities and the capability to meet FDA and HHS
requirements for the conduct of research using investigational
agents.
 
4. Each CNSC, a minimum of five institutions, must have the
demonstrated capability of accruing at least 60-80 fully evaluable,
histologically confirmed high-grade glioma patients per year who
would be appropriate candidates for Phase I or Phase II clinical
trials, and who have acceptable performance status and organ function
to enter such trials. Heavily pretreated patients are not usually
considered appropriate subjects for some phase II studies.  In the
case of a consortium (CNSC) with more than five clinical member
institutions, a minimum of 15 evaluable patients per institution per
year will be required.
 
5. The CNSC must demonstrate an active laboratory program at one or
more of its Participant Member Institutions that utilizes human
glioma specimens or cell lines and would be able to take advantage of
additional clinical specimens (and accompanying clinical data) to
perform correlative studies bearing on the clinical behavior of CNS
tumors and/or their response to therapeutic interventions.
Experience with gliomas and/or other human CNS tumors must be
documented by a record of publications or peer-reviewed grant
support.
 
6. The CNSC must demonstrate laboratory capabilities among one or
more of its Participant Member Institutions sufficient to perform
two-four comprehensive pharmacokinetic studies per year of selected
Phase I or Phase II drugs being evaluated by the consortium.
Experience with pharmacokinetic data analysis and correlation of
these data with clinical drug response must be documented, as must
familiarity with the latest technology for the detection and
quantitation of drugs and their metabolites in physiological fluids
and tissues. (see RESEARCH OBJECTIVES, RESEARCH GOALS AND SCOPE
above)
 
B.  Each Participant Member Institution in the CNSC must have a
mechanism to collect and ship patient specimens to other members of
the CNSC and other consortia under the guidelines established for the
individual studies. Institutions involved in laboratory studies must
have the capability to receive and conduct research studies on
patient specimens not only from within their own centers, but also
from other members of the CNSC and other consortia funded by these
cooperative agreements. There must also be a mechanism in place for
the collection and transfer of patient and laboratory data to the
Central Operations Office/Coordinating Center for analysis.
 
C.  Each institution participating in the clinical trials of the
consortium must meet the following requirements:
 
1.  Experienced full-time physician investigators associated with the
project who have demonstrated expertise in Phase I/II studies.
 
2.  A multi-disciplinary neuro-oncology team with clinician members
representing expertise in the disciplines of medical and radiation
oncology, neurology/neurosurgery, neuropathology and neuroradiology.
 
3.  Adequate physician, nursing and data management resources to
comply with all data reporting requirements of NCI-sponsored Phase I
and II trials.
 
4.  Patient populations to support adequate patient accrual (criteria
determined by the consortium) with annual monitoring to assure
continued enrollment of patients on Phase I and II trials.
 
5.  Availability of state-of-the-art instrumentation for advanced
neuro-imaging and for radiation therapy.
 
6.  Appropriate drug control procedures as required for utilization
of NCI-supplied experimental agents.
 
7. Capability of meeting FDA requirements in A3 above.
 
All costs required for these studies must be included in the
application and must be fully justified.  These costs include the
additional costs of clinical research associated with Phase I and
Phase II studies including costs for patient accrual, sample
handling, laboratory studies, quality assurance, data management and
data analysis, study monitoring, and travel.  Each CNSC should
anticipate the need to attend two meetings per year to share data and
to coordinate activities.  Travel funds for two representatives from
the Central Operations Office/Coordinating Center and one or two
representative(s) from each Participant clinical and/or laboratory
Member Institution should be included in the budget.
 
The RFA label available in the application form PHS 398 must be
affixed to the bottom of the face page.  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 number and title must be typed on line 2a of the face page of
the application form and the YES box must be marked.
 
The Social Security Number (SSN) of the Principal Investigator should
be provided along with the applicant's name at the top of the
Personal Data form page only (PHS Form 398, page KK).  The SSN should
not be listed on the face page of the application, nor provided
elsewhere in the application, e.g., top of each application page.
When submitting competing renewal applications using the PHS 398
grant application kit, do not complete or submit the Personnel Report
form page (JJ).  This form page will be requested, if necessary, at
the time of award.
 
Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact photocopies, in one package:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD 20817 (for express mail)
 
At the time of submission, two additional copies of the application
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 March 13, 1997.  If an application
is received after that date, it will be returned.
 
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.  This does not preclude
the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction
addressing the previous critique.
 
REVIEW CONSIDERATIONS
 
All applications will be judged on the basis of the documented
ability of the investigators to meet the RESEARCH OBJECTIVES of the
RFA as listed under Review Criteria.
 
A.  Review Procedures
 
Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NCI.  Incomplete applications will be
returned to the applicant without further consideration.
Applications that are judged non-responsive will be returned by the
NCI.
 
Applications may be reviewed by an NCI peer review group on the basis
of relative competitiveness.  The NCI will withdraw from further
competition those applications judged to be noncompetitive for award
and notify the applicant and institutional business official.  Those
applications judged to be both competitive and responsive will be
further evaluated, using the review criteria stated below, for
scientific and technical merit by an appropriate peer review group
convened by the Division of Extramural Activities, NCI.  The second
level of review will be provided by the National Cancer Advisory
Board.
 
B.  Review Criteria
 
1.  Applications for the Central Operations Office/Coordinating
Center will be reviewed on the basis of the following criteria:
 
o Scientific, technical, and medical significance and originality of
proposed research as reflected in the protocols, research plans and
strategies that address the clinical and laboratory considerations in
the CNSC as a whole.
 
o Qualifications and research experience of the Project Leader,
Principal Investigators, and the key personnel including, but not
limited to, previous experience with design and administration of
multi-institutional clinical trials and correlative laboratory
studies.
 
o Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the CNSC objectives including:
 
o Adequacy of plans for the development, implementation and analysis
of multi-institutional clinical trials
 
o Adequacy of statistical approach for correlating research studies
with treatment outcomes in clinical trials
 
o Adequacy of the available facilities and data management resources
and personnel.  Evidence of the competence of the Central Operations
Office/Coordinating Center with regard to the mechanisms for CNSC
administration, experimental design, quality control, study
monitoring, data management and reporting, statistical analysis, and
compliance with regulatory requirements.
 
o Demonstration of access to sufficient numbers of evaluable patients
for Phase I and II clinical trials and follow-up by the CNSC (see
Eligibility Requirements) and access to adequately processed tissue
samples from a proportion of these patients.
 
o Adequacy of plans for effective collaboration between laboratory
and clinical investigators and the Central Operations
Office/Coordinating Center within the consortium. Documentation of
commitment of the Program Leader and each Principal Investigator and
of key personnel to the goals of the CNSC.
 
o Adequacy of plans for correlative laboratory studies and evaluation
of the data with respect to treatment administration or treatment
outcome
 
o Plans for effective interaction and coordination among Participant
Member Institutions within the consortium, with other consortia
working on CNS tumors, and with the NCI.
 
2. Applications for Participant Member Institutions will be reviewed
on the basis of the following criteria:
 
o The overall qualifications of applicant institutions to meet the
requirements for participation listed under APPLICATION PROCEDURES.
 
o Scientific merit and feasibility of the proposed research.
 
o Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research.
 
o Demonstration of availability of and access to sufficient numbers
of evaluable patients for the conduct of phase I and II clinical
trials.  Evidence of ability to accrue patients to clinical trials.
 
o Clinical and/or basic research experience, training, time
availability, and research competence of the investigators involved.
 
o Adequacy of plans for pathology support for tumor classification
and for banking and distribution of patient specimens for concurrent
and future studies.
 
o Availability of state-of-the-art imaging equipment, especially MRI.
The availability of MRS, SPECT, PET and other imaging techniques will
be considered favorable additional assets.
 
o Adequacy of state-of-the-art radiotherapy equipment.  The
availability of equipment for stereotactic radiosurgery and
brachytherapy is not required, but would also be considered as assets
to the application.
 
o Adequacy of the available facilities and data management resources.
 
o Adequacy of provisions for the protection of human subjects.
 
o Adequacy of the plans for inclusion of females and minorities.
 
The reviewers will also judge the appropriateness of the proposed
budget and duration in relation to the scientific merit and
feasibility of the proposed research.
 
AWARD CRITERIA
 
Applications considered by the National Cancer Advisory Board will be
considered for award based upon (a) scientific and technical merit;
(b) availability of funds; and (c) programmatic priorities.
Preference will also be given to clinical investigators who are new
to this research area.
 
Letter of Intent Receipt Date:             January 24,1996
Application Receipt Date:                  March 13, 1997
Review by National Cancer Advisory Board:  October 1997
Anticipated Award Date:                    December 1997
 
INQUIRIES
 
Written and telephone inquiries concerning the objectives and scope
of this RFA and inquiries about whether or not specific proposed
research would be responsive are strongly encouraged and may be
directed to program staff listed below.  The program staff welcome
the opportunity to clarify any issues or questions from potential
applicants.
 
Direct inquiries regarding scientific issues to:
 
Dr. Richard Kaplan
Division of Cancer Treatment Diagnosis and Centers
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Boulevard MSC 7436
Bethesda, MD  20892-7436
Telephone:  (301) 496-2522
FAX:  (301) 402-0557
Email:  KAPLANR@DCT.NCI.NIH.GOV
 
For programmatic information:
 
Ms. Diane Bronzert
Division of Cancer Treatment Diagnosis and Centers
National Cancer Institute
Executive Plaza North, room 734
6130 Executive Boulevard MSC 7436
Bethesda, MD 20892-7436
Telephone:  (301) 496-8866
FAX:  (301) 480-4663
Email:  BRONZERD@DCT.NCI.NIH.GOV
 
Direct inquiries regarding fiscal matters to:
 
Ms. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 282
6120 Executive Boulevard MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext. 256
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 the authorization of the Public Health Service Act, Title IV,
Part A (Public Law 78-410, as amended, Public Law 99-158, 42 USC 241
and 285) and administered under HHS grants policies.  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 routine 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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