Release Date:  March 5, 1999 

PA NUMBER:  PA-99-070


National Cancer Institute

Letter of Intent Receipt Date: One month prior to application receipt date
Application Receipt Dates: June 9, September 9, and November 9, 1999; January
9, March 9, May 9, July 9, September 9, and November for 2000 and 2001



Continuing advances in molecular genetics and drug development have led to new
approaches for inhibiting prostate tumor growth either directly or by
impacting the tumor microenvironment.  These agents include new classes of
cytotoxic agents, agents acting via immune-stimulatory effects, agents that
inhibit angiogenesis and metastasis or alter signaling pathways, and agents
targeted specifically to novel prostate cancer cell targets.  At present,
there is a paucity of funding mechanisms targeted to stimulate the transition
of promising and potentially relevant advances in new drug development from
the laboratory into the clinical setting.

The QUICK-TRIAL program is a pilot program to provide investigators with rapid
access to support for pilot, phase I, and phase II prostate cancer clinical
trials and patient monitoring and laboratory studies to ensure the timely
development of new therapeutic approaches. QUICK-TRIAL will provide a new
approach designed to simplify the grant application process and provide a
rapid turnaround from application to funding.  Features include a modular
grant application and award process, inclusion of the clinical protocol within
the grant application, six submission dates per year, and accelerated peer
review  with the goal of issuing new awards within four months of application
receipt.  Inclusion of the complete clinical protocol within the PHS 398 grant
application is intended to simplify the application process by eliminating the
need to duplicate protocol details in the Research Plan section. Investigators
may apply for a maximum of two years of funding support using the
exploratory/developmental (R21) grant mechanism for up to $250,000 direct
costs per year.


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 PA, QUICK-TRIALS for Prostate
Cancer Therapy, 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), or at


Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments and eligible
agencies of the Federal government.  Racial/ethnic minority individuals,
women, and persons with disabilities as well as new clinical investigators are
encouraged to apply as principal investigators.  An application may include
one or more institutions (e.g., individual institutions, consortia, cancer
centers) with established clinical, laboratory, and statistical resources.


Support of this program will be through the National Institutes of Health
(NIH) exploratory/developmental grant (R21) mechanism.  The
exploratory/developmental (R21) grant mechanism is utilized for pilot projects
or feasibility studies to support creative, novel, high risk/high payoff
research that may produce innovative advances in science. The exploratory
grant program provides support for short-term (up to two years) research
projects.  Applications submitted in response to this PA will be limited to
$250,000 direct costs (excludes third party facilities and administrative
costs).  These grants are non-renewable, and continuation of projects
developed under this program will be through the traditional unsolicited
investigator-initiated research grant program.

Applicants will be responsible for the planning, direction, and execution of
the proposed project.  All PHS and NIH grants policies will apply to
applications received and awards made in response to this program
announcement.  The total project period for applications submitted in response
to this PA may not exceed 2 years.

Specific application instructions have been modified to reflect the "MODULAR
GRANT APPLICATION AND AWARD" process which has been adopted by the NIH (see
the NIH Guide, December 15, 1998).  More detailed information about modular
grant applications, including a sample budget narrative justification pages
and a sample biographical sketch, is available via the Internet at url:



Prostate cancer is the most frequent tumor in American men and one of the most
important causes of death.  There have been refinements made in recent years
in the available treatment modalities of surgery, radiation therapy and
androgen deprivation, but few new therapeutic approaches or highly active new
agents have been identified.  Prostate cancer has in the past presented a
number of challenges in clinical trial design.  Moreover, until recently there
were few agents to explore other than hormones and conventional cytotoxics.
Now advances in molecular genetics and drug development have led to new
approaches for inhibiting prostate tumor growth either directly or by
impacting the tumor microenvironment. These approaches  include new classes of
cytotoxic agents, agents acting via immune-stimulatory effects, agents that
inhibit angiogenesis and metastasis or alter signaling pathways, and agents
targeted specifically to novel prostate cancer cell targets.

At present, there are few mechanisms targeted to stimulate the communication
of promising and potentially relevant advances in new drug development from
the laboratory into the clinical setting. Quite frequently the initial stages
of clinical investigation are the most difficult to accomplish.  They are
resource intensive, and to be done well they require laboratory, pharmacology,
and other resource support, as well as substantial personnel effort, none of
which is supported by health benefit programs.  Nonetheless, these early
studies tend to fare poorly in competition for conventional grant support
precisely because they are preliminary and can not serve as the definitive
tests of new approaches.  Even when funding is received, the review and award
cycle may introduce a year or more of delay.  Except where there is an
industrial sponsor with a particular commitment to development of an agent
specifically for prostate cancer, it may take a long time for a promising
approach to get through the initial phase of demonstrating feasibility and
interest, or it may never be well tested in this disease.  NCI recently
published a new initiative entitled Rapid Access for Intervention Development
or RAID  (http://dtp.nci.nih.gov) to support the clinical development of new
agents by providing access to NCI resources for toxicity studies and
formulation and production of new agents for clinical use.  The QUICK-TRIAL
program will serve as an extension of RAID by providing a new initiative with
accelerated peer review and funding to support the clinical and laboratory
costs of early clinical testing to ensure the timely development of new
therapeutic approaches.

Objectives and Scope

The aim of this initiative is to support pilot, phase I, and phase II clinical
trials and associated patient monitoring and laboratory studies for the
treatment of prostate cancer using novel therapeutic approaches.  Prostate
cancer therapeutic trials in human subjects employing new agents and
therapeutic approaches, whether used as a single agent/modality or in
combination, are appropriate.  Phase I clinical trials open to patients with
advanced cancer, but not limited to prostate cancer, will be accepted if there
is a compelling reason why the treatment approach will be of particular
applicability to prostate cancer.  Preference will be given to clinical trials
that include laboratory studies to validate mechanistic hypotheses or clinical
correlates that can meaningfully guide further clinical development.  The
QUICK-TRIAL program may therefore serve as a extension to the RAID program but
may also be used by applicants whose agents have emerged from industry
development programs, where support may only be needed for mechanistic and
correlative laboratory studies.

Applicants to the QUICK-TRIAL program may request support for the conduct of
either the clinical trial, the proposed laboratory studies, or both.  Whether
the studies are focused on the clinical trial or laboratory studies, the grant
application package must include the complete clinical protocol in the Human
Subjects section of the grant application.  Using the protocol as the major
part of the QUICK-TRIAL application is intended to save the applicants the
significant additional labor of repeating the details of the trial in the body
of the grant application.  Where support is sought for the actual clinical
trial, the protocol should be authored by the investigators applying for
QUICK-TRIAL support.  In cases where the investigator seeks support only for
laboratory studies to accompany a trial funded by the company, a protocol
written by the drug sponsor is acceptable.

Support for the conduct of the clinical trial and/or patient monitoring and
correlative laboratory studies that have clinical relevance to the therapeutic
clinical trial may be requested.  A rigorous description of the rationale and
methodology for the laboratory components of the study, as well as a
description of how the results will be analyzed in conjunction with the
results of the clinical trial, should be provided.  Laboratory studies using
patient specimens from the clinical trial may include patient monitoring
studies (i.e., pharmacokinetics, immune response, etc) or clinical correlative
studies that may guide clinical development of the new agent or approach or
identify patient subsets for specific therapies.  Laboratory studies of  the
underlying mechanisms of intervention, the mechanisms of disease pathogenesis,
or surrogate markers of disease activity and therapeutic effect are
encouraged.  Statistical design issues should be addressed in the research
plan for both the clinical protocol and the laboratory analyses.  The proposed
research plan should convince reviewers that the planned studies are well
conceived, that the methodology is solidly grounded and practical for use in a
clinical trials setting, and that the analysis plan is sensible and likely to
be informative.

In order to review and confer awards to applications received in response to
this PA in a timely fashion without delay of the clinical trial, NCI has
developed a pilot project for accelerated review/award.  QUICK-TRIAL will
provide a new approach designed to simplify the grant application process and
provide a rapid turnaround from application to funding.  Features include a
modular grant application and award process, six submission dates per year,
and accelerated peer review with the goal of issuing new awards within four
months of application receipt. Investigators may apply for up to two years of
funding support.  In order to permit rapid turnaround of the grant
applications, IRB approval must be obtained prior to submission of the grant
application.  If FDA IND approval is needed, documentation of IND submission
must be included in the grant submission.  Investigators who intend to use NCI
sponsored drugs must submit a Letter of Intent (CTEP LOI) to the Cancer
Therapy Evaluation Program, NCI, (http://ctep.info.nih.gov/IDB) prior to
grant submission.  The CTEP LOI for requesting drugs should mention your plans
to submit a grant application for this PA.  An approval letter from CTEP
confirming potential drug availability must be received prior to grant
submission.  This is to insure availability of sufficient quantities of drug
and to avoid unjustifiable duplication of studies already in progress.

Because the QUICK-TRIAL program is designed to support novel and innovative
ideas and utilizes the exploratory grant mechanism, preliminary data as
evidence of feasibility are not required.  However, the applicant does have
the responsibility for developing a sound research plan.  Originality of
approach and potential significance of the proposed research are major
considerations in the evaluation.


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 policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

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 20, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994 available on the web at the following URL address: 

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.

Since this PA focuses on prostate cancer, which only occurs in men, required
inclusion of women does not apply.


It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are clear and compelling scientific and ethical reasons not
to include them. This policy applies to all initial (Type 1) applications
submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address:  http://www.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

Since this PA focuses on prostate cancer, which only occurs in adults,
required inclusion of children does not apply.


Prospective applicants are asked to submit, one month before the application
receipt date, 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 PA 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 a subsequent application,
the information that it contains allows NCI staff to estimate the potential
review workload and avoid conflict of interest in the review.  The letter of
intent is to be sent to Ms. Diane Bronzert at the address listed under


Applicants are strongly encouraged to contact the program contact listed under
INQUIRIES with any questions regarding their proposed project.

Applications are to be submitted on the grant application form PHS 398 (rev.
4/98).  Applications will be accepted on the 9th of June, September, and
November for 1999; 9th of January, March, May, July, September, and November
for 2000 and 2001.  Amended applications are due on the same receipt dates. 
Applications kits are available at most institutional offices of sponsored
research and may be obtained from the Division of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge Drive,
MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, Email:
grantsinfo@nih.gov.  Application kits are also available at:


Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided photocopies, in one package
directly to Dr. Suzanne Fisher at the address listed below.


BETHESDA, MD  20892-7720
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional exact copies of the application and
ALL FIVE SETS of any appendix material must also be sent to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636
Bethesda, MD  20892-7399
Rockville, MD  20852 (for express/courier service)


o  FACE PAGE: The title and number of the program announcement must be typed
in line 2 on the face page of the application and the "YES" box must be
marked.  Investigators without prior R29 or R01 support are encouraged to
apply for this PA and to identify their status as a new investigator on the
front of the grant application.  Item 4 MUST include IRB approval date. 
Applications with "pending" IRB approval will be returned without review. 
Items 7a and 7b should be completed, indicating Direct Costs (in $25,000
increments) and Total Costs [Modular Total Direct plus Facilities and
Administrative (F&A) costs] for the initial budget period.  Items 8a and 8b
should be completed indicating the Direct and Total Costs for the entire
proposed period of support.

of the PHS 398.  It is not required and will not be accepted with the

categorical budget table on Form Page 5 of the PHS 398.  It is not required
and will not be accepted with the application.

o  NARRATIVE BUDGET JUSTIFICATION - Use a Modular Grant Budget Narrative page.
See http://www.nih.gov/grants/funding/modular/modular.htm for sample pages.
At the top of the page, enter the total direct costs requested for each year.

o  Under Personnel, list key project personnel, including their names, percent
of effort, and roles on the project. No individual salary information should
be provided.

For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the nearest
$1,000.  List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of key personnel,
and the role on the project.  The total cost for a  consortium/contractual
arrangement is included in the overall requested modular direct cost amount.

Provide an additional narrative budget justification for any variation in the
number of modules requested.  If large patient care costs or drug acquisition
costs are needed and require additional modules, provide a narrative budget
justification documenting budget costs.

o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual's qualifications for a specific
role in the proposed project, as well as to evaluate the overall
qualifications of the research team.  A biographical sketch is required for
all key personnel, following the instructions below.  No more than three pages
may be used for each person.  A sample biographical sketch may be viewed at:

- Complete the educational block at the top of the form page;
- List current position(s) and then previous positions;
- List selected peer-reviewed publications, with full citations;
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years.

o  RESOURCES - Provide a description of the clinical and laboratory facilities
in which the study is to be carried out, including data management resources. 
Provide information on resources provided by the drug sponsor if not at your

o RESEARCH PLAN - Applications in response to this PA should be concise and
substantially shorter than regular grant applications.  ITEMS a-d MAY NOT

Item 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

Item b - Background and Significance - In two pages or less, use this section
to describe (a) how the proposed research will contribute to meeting the goals
and objectives of the PA; and, (b) explain the rationale for the selection of
the general methods and approaches proposed to accomplish your specific aims. 
Do not include background material provided in the clinical protocol document
but you may refer to the appropriate sections/pages of the protocol.

Items c-d - Progress Report/Preliminary Studies, Research Design and Methods -
In twelve pages or less, complete as instructed in the PHS 398 booklet.  TO
be included in the Human Subjects section even if support is only requested
for laboratory studies.) The investigator may use this section to address the

- Preliminary studies pertinent to the application;

- Rationale and hypothesis for the clinical trial and laboratory studies.

- General methods that will be utilized, clinical, laboratory, or both, as
appropriate; reason(s) for selecting these approaches; 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;

- 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); clinical endpoints should be discussed with particular emphasis on
those aspects that may be especially complicated in prostate cancer trials
(e.g., lack of conventionally measurable disease; patients whose only evidence
of disease is biochemical)

- Plans for data management and verification of research data;

- Potential pitfalls in the experimental design and alternative studies that
will be done if the proposed experiments fail.

form(s) must be included.  NIH will treat as confidential any scientific,
preclinical, clinical, or formulation data and information that the sponsor
deems to be proprietary and confidential.  For each trial, provide a Gender
and Minority Inclusion Report in the format provided in the 398 form

IN ADDITION, applicants must insure that the first page of the human subjects
section includes the following information:

1.  IRB approval and date

2a) If NCI-provided agent(s) to be used:  CTEP-assigned LOI # and date of 
CTEP LOI response letter confirming potential availability

2b) If agent(s) will be provided by a company, letter is provided confirming
plans to provide agents and date available

2c) If this protocol is an initial IND-filing study, include date IND
submitted to FDA

2d) None of the above (2a, 2b, or 2c) applies

IRB, NCI/CTEP, or drug company correspondence should be included in the
Appendix, as applicable.

o  CHECKLIST - This page should be completed and submitted with the
application.  If the F&A rate agreement has been established, indicate the
type of agreement and the date. It is important to identify all exclusions
that were used in the calculation of the F&A costs for the initial budget
period and all future budget years.

o APPENDIX - Include a maximum of 5 publications, manuscripts (submitted or
accepted for publication), abstracts, patents, or other printed material
relevant to this project.  Include letters of collaboration from collaborators
or consultants and documentation verifying access of the agents from the
appropriate drug sponsor.

Applications not conforming to these guidelines will be considered
unresponsive to this PA and will be returned without further review.


Applications will be assigned on the basis of established PHS referral
guidelines.  Applications will be evaluated for scientific and technical merit
by an appropriate scientific review group convened by the Division of
Extramural Activities, NCI, in accordance with the standard NIH peer review
procedures.  As part of the initial merit review, all applications will
receive a written critique and undergo a process in which only those
applications deemed to have the highest scientific merit, generally the top
half of applications under review, will be discussed, assigned a priority
score, and receive a second level review by the National Cancer Advisory

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered by the reviewers in assigning the
overall score weighting them as appropriate for each application.  Note that
the application does not need to be strong in all categories to be judged
likely to have a major scientific impact and thus deserve a high priority
score.  For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field forward.

1. Significance.  Does this study address an important problem?  If the aims
of the application are achieved, will this be a worthwhile experiment in
investigating an innovative therapeutic approach?  How will scientific
knowledge be advanced?  What will be the effect of these studies on the
concepts or methods that drive this field?

2. Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas, including
clinical endpoints of relevance to prostate cancer, and consider alternative
tactics?  Have the investigators considered how the pilot study, if
encouraging, could transition into an eventual definitive test of the
therapeutic approach?

3.  Innovation.  Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies for prostate cancer?

4.  Investigator.  Is the investigator appropriately trained and well suited
to carry out this work?  Is the work proposed appropriate to the experience
level of the principal investigator and other researchers (if any)?

5.  Environment.  Are the planned data management resources adequate?  Does
the scientific environment in which the work will be done contribute to the
probability of success?  Do the proposed experiments take advantage of unique
features of the scientific environment or employ useful collaborative
arrangements? Is there evidence of institutional support?

In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:

o The adequacy of plans to include minorities and their subgroups as
appropriate for the scientific goals of the research.  Plans for the
recruitment and retention of subjects will also be evaluated.

o The reasonableness of the proposed budget and duration in relation to the
proposed research

o The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.


Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding decisions: 
Quality of the proposed project as determined by peer review, availability of
funds, and program priority.


Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding 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
Email:  db85g@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Barbara Fisher
Grants Management Branch
National Cancer Institute
Executive Plaza South, Room 242
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 229
FAX:  (301) 496-8601
Email: fisherb@gab.nci.nih.gov

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636
Bethesda, MD  20892-7399
Telephone:  (301) 496-3428
FAX: (301) 402-0275
Email:  TF12W@ NIH.GOV


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
by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 and part 92. 
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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