Full Text CA-94-014


NIH GUIDE, Volume 23, Number 14, April 8, 1994

RFA:  CA-94-014



National Cancer Institute

Letter of Intent Receipt Date:  August 5, 1994
Application Receipt Date:  September 21, 1994


The Cancer Therapy Evaluation Program (CTEP) and the Biological
Response Modifiers Program (BRMP), Division of Cancer Treatment
(DCT), National Cancer Institute (NCI) invites research grant
applications for the conduct of therapeutic clinical trials research
employing new agents, concepts, or strategies for the treatment of
cancer.  This initiative is aimed at drawing new clinical
investigators into this area of research.


The Public Health Service 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 "Healthy People 2000" (Summary
Report:  Stock No. 017-001-00473-1) through the Superintendent of
Documents, Government Printing Office, Washington, DC 20402-9325
(telephone 202/783-3238).


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.

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


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
applications submitted in response to the present RFA may not exceed
four years.

The total direct cost for the four year period may not exceed
$500,000.  The direct cost in any budget period should not exceed
$150,000.  The anticipated award date is July 1995.

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 95.  However, the NCI has plans to re-issue this RFA for funding
in 1996 and 1997.  Future unsolicited competing continuation
applications will compete with all investigator-initiated
applications and be reviewed according to the customary peer review


Approximately $1,500,000 in total costs per year for four years will
be committed to fund specifically applications submitted in response
to this RFA.  It is anticipated that eight new individual awards will
be made.



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.  There is no
specific program available to train the clinical investigators in the
design and conduct of clinical trials and translational research.
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% 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 in the conduct of
translational clinical trials research.

Project Description

The Cancer Therapy Evaluations Program and the Biological Response
Modifiers Program encourage 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 generated by the applicant or others 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.
Investigators are urged especially to address the more difficult
therapeutic challenges, including the most common malignancies (e.g.,
breast, ovarian, prostate).

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.  In such a case, 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 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 new
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines on the Inclusion of Women and Minorities as
Subjects in Clinical Research," which was reprinted in the Federal
Register of March 20, 1994 (59 FR 14508-14513) to correct typesetting
errors in the earlier publication, and reprinted in the NIH GUIDE FOR
GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11.

Investigator may obtain copies from these sources or from the program
staff or contact person listed below.  Program staff amy also provide
additional relevant information concerning the policy.


Prospective applicants are asked to submit, by August 5, 1994, 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
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663


The research grant application form PHS 398, (rev. 9/91) is to be
used in applying for this RFA.  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, Westwood Building, Room 449, Bethesda, MD 20892, telephone
(301) 710-0267; and from the NCI program staff listed under
INQUIRIES.  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 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, exact photocopies, in one package

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two additional copies of the application
must also be sent to:

Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Boulevard
Bethesda, MD  20892

Applications must be received by September 21, 1994.  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 announcement 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.  Application Requirements

The application must include the following documentation to be
considered for review:

o  A draft of the clinical protocol must be included in the Appendix.
Documentation of the status of Human Subjects and IRB approval should
be included.

o  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.


Upon receipt, applications will be reviewed by the Division of
Research Grants (DRG) for completeness and for responsiveness by the
NCI.  Incomplete applications will be returned to the applicant
without further consideration. If the application is not responsive
to the RFA, NCI staff will 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 may be triaged 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

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, particularly, but not exclusively, in the
area of the proposed research.

6.  Availability of the resources necessary to perform research.

7.  Evidence that appropriate steps have been taken to insure the
protection of human subjects.

8.  Evidence that the applicant is in compliance with NIH policies
regarding the inclusion of women and minorities in clinical research
study populations (STUDY POPULATIONS section of this RFA).

The review group will critically examine the submitted budget and
will recommend an appropriate budget and period of support for each
approved application.


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 5, 1994
Application Receipt Date:                  September 21, 1994
Review by National Cancer Advisory Board:  May 1995
Anticipated Award Date:                    July 1995


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 to:

Ms. Diane Bronzert
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663

Direct inquiries regarding programmatic issues using biologics to:

Dr. Toby Hecht
Division of Cancer Treatment
National Cancer Institute
FCRF 1052, Room 253
Bethesda, MD  20892
Telephone:  (301) 846-1098
FAX:  (301) 846-5429

Direct inquiries regarding fiscal matters to:

Ms. Eileen M. Natoli
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
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 Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke-free workplace and promote the non-use
of all tobacco products.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American


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