Full Text CA-96-017
NIH GUIDE, Volume 25, Number 20, June 21, 1996
RFA:  CA-96-017
P.T. 34

  Intervention, Agents for 
  Clinical Trial 

National Cancer Institute
Letter of Intent Receipt Date:  August 30, 1996
Application Receipt Date:  November 8, 1996
The Cancer Therapy Evaluation Program (CTEP), Division of Cancer
Treatment Diagnosis and Centers (DCTDC), National Cancer Institute
(NCI) invites research grant applications to conduct therapeutic
clinical trials research employing new agents, concepts, or
strategies for the treatment of cancer. This initiative is aimed at
encouraging new clinical investigators who have not previously had
independent grant funding to submit research applications in this
area of research.
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), Investigator Grants for Clinical Cancer
Therapy Research, 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).
Applications may be submitted by domestic non-profit and for-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State or local governments, and
eligible agencies of the Federal government.  Applications from
minority and women investigators are encouraged.
Principal investigators should be new to the clinical research field
and should not have been awarded a previous R01 or R29 grant.  An
important principle to remember is that the more extensive the prior
independent research experiences, regardless of funding sources, the
greater likelihood there will be diminished priority for award.
This RFA will use the National Institutes of Health (NIH) individual
research grant (R01) as its funding mechanism.  Responsibility for
the planning, direction, and execution of the proposed project will
be solely that of the applicant.  The total project period for an
application submitted in response to this RFA may not exceed four
The direct cost for the four year period may not exceed $500,000. The
direct cost in any budget period may not exceed $150,000 (not
including indirect costs for collaborating institutions).  The
anticipated award date is July 1997.
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, the award of grants
pursuant to this RFA is contingent upon the continuing availability
of funds for this purpose.
This RFA is a one-time solicitation for new applications for award in
FY 97.  NCI encourages investigators who responded to the previous
solicitation (RFA CA-95-012) to resubmit.  Future unsolicited
competing continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
customary peer review procedures.
Approximately $2,000,000 in total costs per year for each of four
years will be committed to fund applications submitted in response to
this RFA.  It is anticipated that ten new individual awards will be
In the past year, a number of groups have expressed concern over the
declining number of clinical investigators entering and remaining in
academic research.  Clinical investigators are a critical component
in translating new therapeutic agents and modalities from the
laboratory into the clinic.  They must maintain a broad perspective
and knowledge concerning clinical and basic sciences, while
developing new cancer therapies that are hypothesis driven.  They are
highly interactive with basic and clinical researchers in related
disciplines.  This translational clinician is considered distinct
from the clinician who also has a PhD or equivalent training and
concentrates on basic research or the clinician who participates in
cancer research solely by entering patients on clinical trials.
The Clinical Investigations Task Force of the National Cancer
Advisory Board and a sub-committee of the American Association of
Clinical Oncology (ASCO) have both been addressing the problem of the
decreasing number of academic clinical investigators.  One of the
problems identified is the lack of suitable mechanisms for the
training and funding of clinical oriented investigators involved in
translating basic research into new cancer treatments.  The
traditional grants mechanisms (R01, R29) are under-utilized and often
do not fit the needs of young clinical investigators for the support
of clinical trials research.  The R29 grant mechanism requires the
investigator to devote at least 50 percent effort to a five year
project and the yearly budget is limited to approximately $70,000.
Most clinicians have major clinical and teaching responsibilities and
it is impossible to support both the clinical and laboratory
components needed within the budget limitations of an R29 grant.  New
clinical investigators often do not have the publication or research
track record to be competitive for R01 grant support.  Thus, very few
clinical trial research applications are submitted by new clinical
investigators.  DCT would like to reverse this trend and encourage
new clinical investigators, who have not previously received R01 or
R29 grant support, to submit grant applications for the conduct of
translational clinical trials research.
Project Description
The Cancer Therapy Evaluations Program encourages qualified clinical
investigators to develop R01 grant applications for the conduct of
cancer clinical trials research on new therapeutic agents and
modalities.  Grant applications must include clinical trials
involving human subjects and designed to ultimately improve cancer
survival.  The clinical trials must have a strong rationale and be
based upon preclinical data, preferably generated by the applicant or
collaborators, that support the underlying hypotheses.  New clinical
therapeutic trials employing drugs (including differentiating
agents), biologics (including cytokines, antibodies), vaccine
strategies, radiation, or surgery whether used as a single
agent/modality or in combination are appropriate.
Laboratory studies to monitor patients or to study the mechanism of
antitumor effect and resistance should be included.  The laboratory
studies should be in support of the clinical trial, such that their
conduct leads to a greater understanding of the relationship of the
therapy and biological changes in the patient or the mechanism of
action of an anti-tumor response.  Laboratory studies would include
pharmacokinetic studies of cytotoxic, immune-modulating,
differentiation-inducing, and/or targeted therapeutic agents or
relevant pharmacodynamic correlative studies.  Measurement of
particular biological responses would also be desirable particularly
when this information would be relevant to the interpretation of the
success or failure of the therapy in individual patients on the
clinical trial.
It is expected that a significant level of effort, at least 25
percent, will be committed to the research project by the Principle
Investigator.  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 must be
included with the application.
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.
Prospective applicants are asked to submit, by August 30, 1996, 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 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 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 7432
Bethesda, MD  20892-7432
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-8866
FAX:  (301) 480-4663
The research grant application form PHS 398, (rev. 5/95) is to be
used in applying for this RFA.  These forms are available at most
institutional offices of sponsored research and may be obtained from
the Office of Extramural Outreach and Information Resources, 6701
Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301)
710-0267, email: asknih@odrockm1.od.nih.gov.  The RFA label available
in the PHS 398 application form 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 2 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, exact photocopies, in one package
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
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
Bethesda, MD  20852 (for express mail)
Applications must be received by November 8, 1996.  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.
B.  Special Instructions for the Completion of the PHS 398
"Just-in-Time" is an initiative of the National Institutes of Health
(NIH) Extramural Reinvention Laboratory under the auspices of the
National Performance Review and government-wide efforts to create a
government that works better and costs less.  JIT postpones the
collection of certain information that currently must be included in
all competing applications when submitted. The information for the
applications with a likelihood of funding is submitted "just-in-time"
for awards to be made.  This delayed exchange of information
significantly relieves the administrative burden for the 75 to 80
percent of applicants who will not receive an award.  In addition,
the information that is exchanged "just-in-time" for award will be
current, rather than several months old as is currently the case
(which often necessitates a request for updated information, e.g.,
for other support).
In responding to the RFA, the following are specific instructions for
sections of the PHS 398 application form (rev. 9/95) that should be
completed differently from usual.  Some sections are modified and
others in the application do not need to be completed for the
submission of the application but WILL be requested if your
application receives a priority score in the fundable range.  For all
other items in the application, follow the usual instructions on
pages 5-20 of the PHS 398 booklet.
FACE PAGE (Form AA) - The title and number of the RFA must be typed
in line 2a.  Failure to do so could result in delayed processing of
your application such that it may not reach the review committee in
time for review.
Enter direct costs only for the following:
o  Personnel, Patient Care Costs, Alterations-Renovations - Complete
these sections as instructed in the PHS 398 booklet.
o  Consultant Costs - Itemize only if proposed consultant costs
exceed $10,000 or if a consultant is identified as key personnel.
o  Equipment - Itemize only individual equipment items in excess of
o  Supplies - Itemize (a) all animal costs and (b) any individual
supply item which costs more than $10,000. If animals are involved,
state their unit purchase and care costs.  Enter total animal costs
and supply costs on separate lines.
o  Travel and Other Expenses - Itemize any expense category that
exceeds $5,000.
Do not complete the categorical budget table on form page 5 in the
PHS 398 (rev. 5/95).  Only the requested total direct costs for each
year and total direct costs for the entire proposed period of support
should be shown.   Begin the budget justification in the space
provided, using continuation pages as needed.
Budget Justification
o  List the name, role on project and percent effort for all project
personnel (salaried or unsalaried) and provide a narrative
justification for each person based on his/her role on the project
and proposed level of effort.
o  Identify all consultants by name and organizational affiliation
and describe the services to be performed.
o  Provide a narrative justification for any major budget items,
other than personnel, that are requested for the conduct of the
project that would be considered unusual for the scope of research.
No specific costs for items or categories should be shown.
o  Indirect costs will be calculated at the time of the award using
the institution's actual indirect cost rate.  Applicants will be
asked to identify the indirect cost exclusions prior to award.
o  If consortium/contractual costs are requested, provide the
percentage of the subcontract total costs (direct and indirect)
relative to the total direct costs of the overall project.  The
subcontract budget justification should be prepared following the
instructions provided above.
A biographical sketch is required for all key personnel, following
the modified instructions below.  Do not exceed the two page limit
for each person.
o  Complete the education block at the top of the form page.
o  List current position(s) and those previous positions directly
relevant to the application.
o  List selected peer-reviewed publications directly relevant to the
proposed project, with full citation.
o  Provide information on research projects completed and/or research
grants participated in during the last 5 years which are relevant to
the proposed project.  Title, principal investigator, funding source,
and role on project must be provided.  Please state whether you have
previously served as Principal Investigator on a R01 or R29 grant.
FORM GG - PAGE 7 - OTHER SUPPORT - Do not complete.  Updated
information will be requested by NCI staff from only those applicants
being considered for funding.
Applications in response to this RFA should be concise and shorter
than regular grant applications.  Items a-d may not exceed 20 pages
in total.
a.  Specific Aims - In one page or less, list in priority order, the
broad, long-range objectives. Describe concisely and realistically
the hypothesis to be tested and what the specific research described
in this application is intended to accomplish.
b.  Background and Significance - In two to three pages, use this
section to describe (a) how the proposed research will contribute to
meeting the goals and objectives of the RFA; and, (b) explain the
rationale for the selection of the general methods and approaches
proposed to accomplish your specific aims.
c-d.  Progress Report/Preliminary Studies, Research Design and
Methods - In seventeen pages or less, complete as instructed on pages
20-21 of the PHS 398 booklet with the modification that the clinical
protocol(s) and up to six publications, manuscripts submitted or
accepted for publication, patents, or invention reports can be
included in the Appendix (see below).
Investigator may use this section to address the following:
o  preliminary studies pertinent to the application;
o  rationale and hypothesis for the clinical trial and laboratory
o  general methods that will be utilized; provide specific details
for those techniques which are unique or where a significant
departure from a generally accepted technique is important for
reviewers to know;
o  outcome measures that will be used to assess the success or
failure of each set of experiments (include statistical analyses for
laboratory and clinical studies);
o  plans for the rigorous data management and verification of
research data;
o  potential pitfalls in the experimental design and alternative
studies that will be done if the proposed experiments fail.
Items e-f - Human Subjects, Vertebrate Animals - Complete as
described on pages 17-18.  State clearly the plans for early
detection of and protection against adverse effects on human
subjects.  Documentation for the composition of the proposed study
population in terms of gender and racial/ethnic group together with a
rationale for its choice must be included in the Human Subjects
section (see page 30 for format).
APPENDIX (Page 19) - Up to 10 publications, manuscripts submitted or
accepted for publication, patents, and invention reports may be
provided.  Clinical protocol(s) must be included in this section.
CHECKLIST (Page 19) - Do not submit the checklist page.  For amended
applications, applicants must complete the block in the upper right
corner of the face page to indicate the previous grant number.  A
completed checklist will be required prior to award.
Questions regarding these instructions may be directed to the program
staff listed under INQUIRIES.
Upon receipt, applications will be reviewed by the Division of
Research Grants (DRG) for completeness and by the NCI for
responsiveness.  Incomplete applications will be returned to the
applicant without further consideration.  If the application is not
responsive to the RFA, NCI staff may contact the applicant to
determine whether to return the application to the applicant or
submit it for review in competition with unsolicited applications at
the next review cycle.
Applications that are complete and responsive to the Request for
Applications 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.  As part of the initial merit
review, all applications will receive a written critique and may
undergo a process in which only those applications deemed to have the
highest scientific merit will be discussed, assigned a priority
score, and receive a second level review by the National Cancer
Advisory Board.
The review group will assess the scientific merit of the studies
using the following review criteria:
1.  Importance, timeliness, and clinical merit of the clinical
2.  Quality of data supporting the proposed clinical trial.
3.  Scientific and technical merit of the proposed laboratory
4.  Relevance of the proposed laboratory studies to the clinical
5.  Research training and clinical qualifications of the Principal
Investigator and staff in the area of the proposed research.
6.  Availability and quality of the resources necessary to perform
7.  Quality of data verification and management plans and statistical
The initial review group will critically examine the submitted budget
and will recommend an appropriate budget and period of support for
each approved application.  They will also examine the provisions for
the protection of human and animal subjects, the safety of the
research environment, and conformance with the NIH Guidelines for the
Inclusion of Women and Minorities as Subjects in Clinical Research.
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:             August 30, 1996
Application Receipt Date:                  November 8, 1996
Review by National Cancer Advisory Board:  May 1997
Anticipated Award Date:                    July 1997
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. The program
staff welcome the opportunity to clarify any issues or questions from
potential applicants.
Direct inquiries regarding general programmatic issues and
chemotherapy agents to:
Ms. Diane Bronzert, Program Director
Division of Cancer Treatment, Diagnosis, and Centers
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Boulevard MSC 7432
Bethesda, MD  20892-7432
Telephone:  (301) 496-8866
FAX:  (301) 480-4663
Direct inquiries regarding fiscal matters to:
Ms. Eileen M. Natoli
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Boulevard MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext. 256
FAX:  (301) 496-8601
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 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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