Subject: NIH GUIDE - RFA CA-91-16 - V20(20) 05/24/91
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 22 May 91 17:20 EST

Hi Paul,
  Please post to the NIH Listserver as:
     RFACA-91-16.910524
                       Thanks.  dottie
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA CA9116 CA-91-16 **********************************************
 
REQUEST FOR APPLICATIONS
 
RFA:  CA-91-16
 
NEW THERAPEUTIC APPROACHES TO THE TREATMENT OF PROSTATE CANCER
 
P.T. 34; K.W. 0715035, 0705075, 0745070, 0755015, 0760020, 0760025
 
National Cancer Institute
 
Letter of Intent Receipt Date:  July 22, 1991
Application Receipt Date:  October 15, 1991
 
I. PURPOSE
 
The Division of Cancer Treatment (DCT) of the National Cancer Institute
(NCI) invites research grant applications (R01) from interested
investigators to perform clinical studies in prostate cancer to improve
treatment results and clinical outcome.  Investigators are encouraged to
utilize laboratory advances in understanding tumor growth and hormonal
control in prostate cancer to develop an integrated research program of
laboratory experimentation and concurrent clinical studies.  New and
experienced investigators in relevant fields and disciplines may apply
for funds to support therapeutic clinical studies.
 
The present Request for Applications (RFA) announcement is for a single
competition with a specified application deadline of October 15, 1991.
The NCI anticipates making three to four awards for project periods of
up to three years.  A total of $750,000 has been set aside for funding
these activities in the initial year.
 
The 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, New Therapeutic
Approaches to the Treatment of Prostate Cancer, 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, D.C. 20402-9325 (telephone 202-783-3238).
 
Applications must be prepared and submitted in accordance with the aims
and requirements described in the following sections.
 
II.  BACKGROUND INFORMATION
 
The incidence of prostate cancer continues to increase each year and has
now surpassed lung cancer to become the most common carcinoma in males.
It is estimated that approximately 122,000 new cases will be diagnosed
in 1991 accounting for 19 percent of all male cancers.  Black men in the
United States have the highest rate of prostate cancer in the world.  At
the time of clinical presentation, more than 50 percent of newly
diagnosed patients will have either locally advanced or metastatic
disease.  Prostate cancer is the second leading cause of death from
neoplasia among American men causing more than 32,000 deaths in 1990.
It is an important cause of morbidity and mortality in the elderly.
These upward trends are expected to continue as the male population
ages.
 
If prostate cancer is diagnosed early while still confined to the
prostate, the disease is curable with radical prostatectomy or radiation
therapy.  For patients with more advanced stages, initial treatment is
based on presumed hormonal dependence of prostatic cancer cell growth
and includes surgical and diethylstilbestrol castration.  In recent
years, new methods of hormone treatment utilize pharmacologic agents
capable of reducing or blocking the action of testosterone, the major
circulating androgenic hormone, by interrupting the complex interactions
among the hypothalamus, pituitary, testis, and adrenal glands.
Leuprolide and goserelin (Zoladex) are two LH-RH analogs recently
approved for clinical use that produce a medical castration.  Flutamide
is a synthetic nonsteroidal antiandrogen that has also shown promise in
clinical trials.  However, these new therapeutic agents do not prevent
the emergence of hormone-resistant cells.  Advanced prostate cancers
ultimately fail to respond to androgen deprivation.  The mechanisms
involved in the loss of androgen dependence are not understood.  There
is no alternative therapy that can be offered at present to these
patients that consistently results in reduction in tumor mass or
palliation of symptoms.
 
In recent years, basic researchers have made promising new advances in
understanding the mechanisms of growth control in the human prostate
cell.  The growth and differentiation of benign and malignant prostatic
epithelial cells are regulated by androgens that in turn are modulated
by growth factors and other hormones.  A production of growth factor
activities like Transforming Growth Factor beta, Transforming Growth
Factor alpha, and Epithelial Growth Factor have been demonstrated in
prostate cancer cell lines.  Clinical trials utilizing suramin, which
interferes with heparin-binding growth factors, have recently shown
responses in advanced prostate cancer.  The mechanism of action of
suramin is still not completely understood and ancillary laboratory
studies are needed.  In addition, biological response modifiers in
combination with chemotherapy have achieved promising results in other
tumor models but have not been adequately explored in prostate cancer.
Recent advances in understanding the molecular and cellular mechanisms
operative in resistance to chemotherapy have led to the design of new
therapeutic strategies to overcome drug resistance in other tumors.
Many opportunities exist to develop new treatment strategies in prostate
cancer utilizing laboratory advances in understanding tumor growth and
hormonal control.
 
III.  RESEARCH GOALS AND SCOPE
 
The major goal of this RFA is to foster interactions between basic
science laboratories and clinicians performing clinical trials for
patients with prostate cancer.  Investigators are encouraged to propose
pilot therapeutic clinical studies or new clinical trials (Phase I, II,
or III) designed to improve therapy in prostate cancer patients.  The
application may include ancillary laboratory studies linked to the
clinical trial.  Applications must be focused on integrating clinical
goals with laboratory research areas.
 
This RFA envisions funding therapeutic clinical studies that test and
exploit basic findings concerning cellular targets of treatment or
response to drug or hormone therapies.  Clinical studies should involve
human subjects and be designed to improve cancer treatment.  Examples of
clinical studies include:  (1) growth factor or hormone therapies
utilizing new agents; (2) treatment therapies for overcoming hormone,
drug, or radiation resistance; (3) treatment therapies based on novel
mechanisms of action; (4) biologics in combination with drug or
radiation regimens; (5) new therapies combining endocrine manipulations
with chemotherapeutic agents; and (6) radiation modifiers to enhance
cell kill or protect normal tissue.
 
Laboratory research studies that are relevant to the therapeutic
clinical studies may be included.  Investigators already participating
in relevant clinical trials are encouraged to develop related
complementary laboratory studies.  Laboratory experimentation may be
designed to examine mechanism of action, mechanism of resistance, or
conduct pharmacological analysis of the antitumor agents utilized in the
patient studies.  Laboratory studies designed to improve diagnosis or
studies examining benign prostate disease are not applicable.
 
Examples of therapeutic correlates that would be measured in patients or
tumors include:  (1) hormone or growth factor receptor alterations that
correlate with the development of hormone resistance; (2) studies of
phenotypic or genotypic alterations correlated with drug or radiation
resistance; (3) correlation of tumor growth factors or oncogenes with
response to growth factor targeted therapies; (4) pharmacokinetic and
pharmacodynamic studies; and (5) biochemical pharmacologic analysis.
Investigators are not limited to the above areas of potential studies.
Analysis of potential racial differences in clinical and laboratory
parameters must be considered.
 
IV.  MECHANISM OF SUPPORT
 
Support of the program will be through the National Institutes of Health
(NIH) grant-in-aid (R01).  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.  Most likely continuation
applications will compete with all investigator-initiated applications
and be reviewed by the Division of Research Grants (DRG).  However, if
the NCI determines that there is a sufficient continuing program need, a
request for competitive continuation applications will be announced.
Only recipients of awards under this RFA will be eligible to apply.
 
Approximately $750,000 in total costs per year for three years will be
committed to fund applications submitted in response to this RFA.  It is
anticipated that three to four awards will be made.  Applications with
requested budgets greatly exceeding these general parameters may be at a
disadvantage with respect to final funding decisions.  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 must not exceed three years.
The earliest feasible start date for the initial award will be July 1,
1992.  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 REQUIREMENTS
 
Non-profit organizations and institutions, governments and their
agencies, and individuals are eligible to apply.  For-profit
organizations are also eligible unless specifically excluded by
legislation.  Both domestic and foreign applicants may apply.
Applications may be submitted from a single institution or may include
arrangements with multiple institutions (e.g., consortia and Clinical
Trials Cooperative Group) if appropriate.
 
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.  Evaluation for responsiveness to the RFA is an
NCI program staff function.  Applications will be judged to determine
how well they meet the goals and objectives of the program as described
in the RFA.  Applications that are judged non-responsive will be
returned to the applicant but may be submitted as investigator-initiated
research grants at the next receipt date.  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 NCI will conduct a preliminary
scientific peer review to eliminate those that are clearly not
competitive.  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 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.  Significance and originality of the research from a scientific and
technical viewpoint.
 
2.  Feasibility of proposed research.
 
3.  Adequacy and appropriateness of the methodology and protocol design.
 
4.  Clinical and diagnostic pathological experience, training, time
availability, and research competence of the investigators involved.
 
5.  Adequacy of available resources and environment (facilities,
equipment, statistical collaboration, patient population, specimens, and
others).
 
6.  Provision for the adequate protection of human subjects.
 
7.  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.  If the clinical trial is funded through another source and
the investigator is only asking for support for laboratory
investigations, this should be clearly outlined.
 
C. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
 
The following is a statement of NIH and ADAMHA policies concerning
inclusion of women and minorities in clinical research study
populations.  The inclusion of women is standard terminology for all
grants and contracts; however, due to the specific subject of this RFA
(prostate cancer), it is not applicable under this RFA.
 
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.
Appli-cants/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 popula-tions (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; from the Office of Grant Inquiries,
Division of Research Grants, National Institutes of Health, Room 449,
Westwood Building, 5333 Westbard Avenue, Bethesda, MD 20892; and from
the NCI Program Director named below.
 
The RFA label available in the 10/88 revision of 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 2 of the face page of the
application form.
 
Submit a signed, typewritten original of the application, including the
Checklist, and four 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 additional copies of the application must
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 October 15, 1991.  If an application is
received after that 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
that 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 July 22, 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 is 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) 480-4663
 
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 and 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.
 
Written and telephone inquires of a budgetary, administrative, and/or
policy nature should be directed to:
 
Ms. Carolyn Mason
Grants Management Specialist
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Blvd.
Bethesda, MD  20892
Telephone:  (301) 496-7800, extension 59
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 Sections 301,
410, and 411, Part A (Public Law 78-410, 42 USC 241 as amended, Public
Law 99-158, 42 USC 285a) and administered under PHS grant policies and
Federal Regulations at 42 CFR Part 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.