Subject: RFA CA-91-03.901228
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 27 Dec 90 08:12 EST

Good Morning Paul,
   I hope you and your had a Very Merry Christmas and Happy Holidays,
etc.  Welcome back after a long weekend.
   There will be several items for posting today for the l2/28/90
NIH Guide.  However, only two of them have arrived so far.  Please post
this one to the NIH Listserver as:
         RFACA-91-03.901228
   Thanks.
          Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR APPLICATIONS
 
RFA NUMBER:  CA-91-03
 
CLINICAL TREATMENT AND CORRELATES OF UPPER GI
CARCINOMA
 
P.T. 34; K.W. 0715035, 0715085
 
National Cancer Institute
 
Letter of Intent Date:  February 25, 1991
Application Receipt Date:  April 8, 1991
 
I. PURPOSE
 
The Division of Cancer Treatment (DCT) of the National Cancer
Institute (NCI) invites research grant applications (R01) from
interested investigators to assess new clinical correlates and
develop new treatment modalities in upper gastrointestinal (GI)
carcinoma by means of an integrated research program of
laboratory experimentation and concurrent clinical trials.  New,
as well as experienced, investigators in relevant fields and
disciplines may apply to fund new therapeutic clinical trials or
new correlative laboratory studies that are related to clinical
trials.
 
The present Request for Applications (RFA) announcement is for a
single competition with a
specified deadline of April 8, 1991, for receipt of applications.
Applications should be prepared and submitted in accordance with
the aims and requirements described in the following sections:
 
I.    PURPOSE
II.   BACKGROUND INFORMATION
III.  RESEARCH GOALS AND SCOPE
IV.   MECHANISM OF SUPPORT
V.    ELIGIBILITY
VI.   REVIEW PROCEDURES AND CRITERIA
VII.  METHOD OF APPLYING
VIII. LETTER OF INTENT
IX.   INQUIRIES
 
II. BACKGROUND
 
Carcinoma of the organs of the upper GI tract
(esophagus and stomach) are lethal tumors.  Development of
resistance to treatment (as manifested by tumor progression) is
rapid even when chemotherapy, with or without radiation therapy, is
effective.  Taken collectively, the incidence of these tumors
represents a major health hazard to 35,000 patients per year.
Adenocarcinoma of the esophagus formerly was a rare tumor (8-11%
of esophageal cases), but recent clinical reports suggest that
approximately 30% of esophageal cancer patients annually are now
presenting with adenocarcinoma (associated with Barrett's
esophagus).  If these figures are representative of a wider
epidemiologic shift, up to 3,000 cases of esophageal
adenocarcinoma may occur each year.  In addition, there are
24,000 cases of gastric carcinoma and 8,000 cases of esophageal
squamous carcinoma annually.  Except for the 11% of patients with
gastric cancer limited to the stomach, who are able to undergo
curative resection, and a similar group of patients with
esophageal cancer, the average life span for patients with these
cancers is 4 to 6 months.  The reported response rates for
cytotoxic therapy range from 5% to 40%.  Relatively few complete
responses are noted and no patient with metastatic disease is
cured.  Recently, however, promising results utilizing
combinations of radiation or surgery and chemotherapy have been
reported for esophageal cancer.
 
The NCI supports basic research efforts to describe and
understand the tumor biology and treatment resistance of
malignancies.  Such efforts form the basis for the development of
new treatment modalities.  Relatively few investigations are
supported in upper gastrointestinal carcinoma to move new
advances in the laboratory into the clinic.  This RFA encourages
applicants to address their research efforts towards the upper GI
carcinomas and the development of new clinical therapies.  For
example, monoclonal antibodies directed against gastrointestinal
tumor-specific antigens have been developed, characterized, and
applied for diagnostic purposes.  The potential of these
antibodies to improve clinical management and/or therapy of these
diseases needs further investigation.  Clinical correlations of
oncogenes, growth factors, or markers of drug resistance may
prove useful in subsets of patients that would respond to
specific treatment therapies.
 
III.  RESEARCH GOALS AND SCOPE
 
The major goal of this RFA is to foster interactions between
basic science laboratories and clinicians performing clinical
trials in upper GI carcinoma to improve treatment results and
clinical outcome.  To accomplish this goal, two types of studies
will be supported: (1) the development of new therapeutic
clinical trials or (2) new correlative studies relevant to
clinical trials.  Applications should be focused on integrating
clinical goals with laboratory research areas.
 
This RFA envisions funding new therapeutic clinical trials in
upper GI carcinomas that test and exploit basic findings
concerning drug resistance or cellular targets of treatment.
Clinical studies should be designed to improve cancer treatment.
New clinical studies dealing with treatment using
chemotherapeutic drugs, biologics, radiation, or surgery, whether
used as a single agent/modality or in combination, are
appropriate.  Examples of clinical trials based on new
therapeutic approaches include: (1) treatment therapies for
overcoming drug or radiation resistance; (2) treatment therapies
based on novel mechanisms of action; (3) biologics in combination
with drug or radiation regimens; (4) immunotherapies including
monoclonal antibody therapy, radioimmunotherapy, and the use of
new immunotoxins; (5) new therapies combining endocrine
manipulations with chemotherapeutic agents; (6) more effective
combinations of chemotherapy and radiation therapy; or (7)
radiation modifiers to enhance cell kill or protect normal
tissue.
 
This RFA has a second research goal of funding new correlative
laboratory studies that are relevant to therapeutic clinical
trials.  Some examples of therapeutic correlates include:  (1)
phenotypic or genotypic alterations which appear to correlate
with the development of drug or radiation resistance; (2)
oncogenes, growth factors, and specific antigen expression on
tumor cells for antibody development; (3) pharmacokinetic and
pharmacodynamic measurements; and (4) biochemical pharmacologic
parameters.  The therapeutic correlates must have a future
clinical application such as development of new treatment
strategies or identification of patient subsets for specific
treatment therapies.  This RFA does not support research
investigations on diagnostic markers or clinical correlates which
will have no impact on the clinical treatment of patients.  The
laboratory assays must utilize patient specimens from new or
ongoing clinical trials and have been demonstrated to be
applicable to tissue samples and/or body fluids, etc.
Investigators are encouraged to obtain patient specimens from
multi-institutional clinical trials to ensure adequate sample
size for statistical analysis.
 
Research investigators are not limited to the above areas of
potential studies.  Clinical protocols should be included in the
Appendix of the application.  A section on statistical support
should be included in the grant application to ensure proper
correlation of assay parameters with clinical outcome.
 
IV.  MECHANISM OF SUPPORT
 
Support of the program will be through the National Institutes of
Health (NIH) grant-in-aid (RO1).  Applicants will be responsible for
the planning, direction, and execution of the proposed project.
Except as otherwise stated in this
RFA, awards will be administered under PHS grants policy as
stated in the Public Health Service Grants Policy Statement, DHHS
Publication No. (OASH) 90-50,000, revised October 1, 1990.
 
This RFA is a one-time solicitation.
 
Approximately $1,500,000 in total costs per year for three years
will be committed to specifically fund applications that are
submitted in response to this RFA.  It is anticipated that 6 to 8
awards will be made.  This funding level is dependent on the
receipt of a sufficient number of applications of high scientific
merit.  The total project period for applications submitted in
response to the present RFA should not exceed three (3) years.
The earliest feasible start date for the initial award will be
December 1, 1991.  Although this program is provided for in the
financial plans of the NCI, the award of grants pursuant to this
RFA is also contingent upon the continuing availability of funds
for this purpose.
 
V.  ELIGIBILITY
 
Non-profit and for-profit, domestic organizations and
institutions, governments and their agencies are eligible to
apply.
Applications can be from single institutions or multiple
institutions (collaborating institutions, consortia, cooperative
groups).  We encourage new, as well as experienced,
investigators to apply.
 
VI.  REVIEW PROCEDURES AND CRITERIA
 
A.  REVIEW PROCEDURE
 
Upon receipt, applications will be reviewed by the DRG for
completeness.  Incomplete applications will be returned to the
applicant without further consideration.  Applications will be
evaluated by NCI Program staff to determine whether they are
responsive to this RFA and meet the stated goals and objectives
of the program.  Applications that are judged non-responsive
will be returned to the applicant.  Questions concerning the
relevance of proposed research to the RFA should be directed to
program staff as described in the INQUIRIES section.
 
In cases where the number of applications is large compared to
the number of awards to be made, the NIH will conduct a
preliminary scientific peer review to eliminate those that are
clearly not competitive.  The NIH will remove from 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 by the National Cancer Advisory
Board considers the special needs of the Institute and the
priorities of the National Cancer Program.
 
B.  REVIEW CRITERIA
 
The factors considered in evaluating the scientific merit of each
response to this RFA will be:
 
1. Extent to which the proposed research addresses the goals of
the RFA.
 
2. Significance and originality of the research from a scientific
and technical viewpoint.
 
3. Feasibility of proposed research.
 
4. Adequacy and appropriateness of the methodology and protocol
design.
 
5. Clinical experience, training, time availability, and research
competence of the investigators involved.
 
6. Adequacy of available resources and environment (facilities,
equipment, statistical collaboration, patient population, etc.).
 
7. Provision for the adequate protection of human subjects.
 
8. Documentation of support from collaborators and consultants
through letters of commitment.
 
The review group will critically examine the submitted budget and
will recommend an appropriate budget and period of support for
each approved application.
 
C.  SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that
research findings can be of benefit to all persons at risk of the
disease, disorder or condition under study; special emphasis
should be placed on the need for inclusion of minorities and
women in studies of diseases, disorders and conditions which
disproportionately affect them.  This policy is intended to apply
to males and females of all ages.  If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear
compelling rationale should be provided.
 
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group.  In
addition, gender and racial/ethnic issues should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study.  This information should be
included in the form PHS 398 in Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility
of including the broadest possible representation of minority
groups.  However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
 
The rationale for studies on single minority population groups
should be provided.
 
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including but not limited to
clinical trials.
 
The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
 
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
 
If the required information is not contained within the
application, the application will be returned.
 
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies.  If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
 
All applications for clinical research submitted to NIH are
required to address these policies.  NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
 
VII. METHOD OF APPLYING
 
The research grant application form PHS-398 (revised 10/88)
must be used in applying for these grants.  These forms are
available at most institutional business offices; the
Office of Grant Inquiries, Division of Research Grants, National
Institutes of Health, Room 449, Westwood Building, 5333 Westbard
Avenue, Bethesda, MD 20892; and the NCI Program Director
named below.
 
The RFA label available in the 10/88 revision of Application Form
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
should be typed on line 2 of the face
page of the application form.
 
Submit a signed, typewritten original of the application,
including the Checklist, and four (4) signed, exact photocopies,
in one package to the Division of Research Grants at the address
below.  The photocopies must be clear and single sided.
 
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
At the time of submission, two (2) additional copies of the
application should also be sent to:
 
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 848
5333 Westbard Avenue
Bethesda, MD 20892
 
Applications must be received by April 8, 1991.  If an
application is received after the indicated date, it will be
returned.  If the application submitted in response to this RFA
is substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one.  Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this
RFA which is essentially identical to one that has already been
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.
 
VIII. LETTER OF INTENT
 
Prospective applicants are asked to submit by February 25, 1991, a
letter of intent that includes a descriptive title of the
proposed research, the name and address of the Principal
Investigator, the names of other key personnel, the participating
institutions, the number and title of the RFA in response to
which the application is being submitted.
 
Although a letter of intent is not required, is not binding, and
does not enter into the review of subsequent applications, it is
requested in order to provide an indication of the number and
scope of applications to be reviewed.
 
The letter of intent should be sent to:
 
BY US POSTAL
 
Ms. Diane Bronzert
Program Director
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 496-9384
 
BY DIRECT DELIVERY
 
Ms. Diane Bronzert
Program Director
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Blvd.
Rockville, MD  20852
 
IX. INQUIRIES
 
Written or telephone inquiries concerning the objectives and
scope of this RFA or inquiries about whether or not specific
proposed research would be responsive are encouraged and should
be directed to Ms. Diane Bronzert at the above address.  The
program director welcomes the opportunity to clarify any issues
or questions from potential applicants.
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.395, (Clinical Treatment Research).  Awards are
under authorization of the Public Health Service Act, Title IV,
Part A (Public Law 78-410, as amended by Public Law 99-158, 42
USC 241 and 285) and administered under PHS Grant Policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74.  This program
is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.