NIH GUIDE, Volume 21, Number 17, May 8, 1992

PA NUMBER:  PA-92-76

P.T. 34





  Biological Response Modifiers 

  Growth Factors 

National Cancer Institute

National Institute of Allergy and Infectious Diseases


The Division of Cancer Treatment (DCT) of the National Cancer Institute

(NCI) and the Division of Acquired Immunodeficiency Syndrome (DAIDS) of

the National Institute of Allergy and Infectious Diseases (NIAID)

invite applications from interested investigators to perform innovative

correlative laboratory studies of relevance to new and ongoing AIDS-

Kaposi's sarcoma clinical trials or to develop new therapies for the

treatment of AIDS-Kaposi's sarcoma with laboratory correlations.  This

Program Announcement (PA) is designed to promote collaborations and

interactions among researchers from a variety of basic and clinical

disciplines to facilitate better treatment and management of AIDS-

Kaposi's sarcoma patients.


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, AIDS-

Associated Kaposi's Sarcoma, 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 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.  Foreign institutions

are not eligible for the First Independent Research Support and

Transition (FIRST) (R29) Award.  Applications from minority individuals

and women are encouraged.  Applications from single or multiple

institutions (individual institutions consortia, and cancer centers)

with established clinical, laboratory, and statistical resources are



Awards will be made as investigator-initiated research grants (R29, R01

and interactive R01s) in accordance with PHS policies applicable to

research project grants.  A description of an interactive R01

application is published in the NIH Guide (Vol. 21, No. 1, January 10,

1992) under PA-92-29.  Responsibility for the planning, direction, and

execution of the proposed research will be solely that of the

applicant.  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.



Kaposi's Sarcoma (KS) is one of the malignancies most frequently seen

in AIDS patients; however, the etiology of KS in AIDS patients remains

unclear.  The precise relationship of KS to the underlying

immunodeficient state in patients with HIV infection also remains

unclear.  The most prominent clinical feature of KS in HIV-positive

patients is the aggressiveness of the disease. KS in AIDS patients is

associated with extensive involvement of skin and mucous membranes,

early dissemination to lymph nodes, impressive development of extreme

lymphedema, even in the absence of bulky adenopathy, and rapid spread

to visceral organs, including lungs and gastrointestinal tract.

Although rapid clinical progression and short median survival have been

the rule, some patients have survived for many years with disease

limited to the skin. Certain clinical and laboratory features, such as

presence of unexplained fever, night sweats, weight loss, and

significant T4 lymphocytopenia, have been identified as indicators of

poor prognosis. Various therapeutic interventions have been employed

resulting in partial and complete remissions but with no significant

improvement in the survival of these patients.  High-dose recombinant

interferon alpha has produced response rates in approximately 30

percent of treated patients.  Likewise, vinblastine has produced

similar response rates.  Both of these therapies have substantial toxic

side effects.  The purpose of this PA is to foster collaborative

interactions between laboratory scientists and clinicians to precisely

characterize the molecular and genetic characteristics of AIDS-

Kaposi's Sarcoma or to devise more effective management of this

disease.  Laboratory research efforts and novel therapies ready to be

applied in clinical situations and innovative clinical applications are

solicited.  It is hoped that the results obtained from studying AIDS-

Kaposi's sarcoma patients will increase the understanding of the

biology of this disease and will assist the development of more

effective treatment in the general population of KS patients and

patients with other proliferative diseases.

Some examples of clinical studies and their correlative laboratory

studies that would qualify are:  (l) pharmacokinetic and

pharmacodynamic measurements leading to novel means of combining

retroviral and antitumor therapies; (2) biological response modifiers

in combination with cytotoxic and radiation therapy with immune

function studies; (3) molecular characterization of oncogenes and

growth factors for the development of new anti-growth factor or anti-

sense therapies. Investigators are not limited to the above examples of

potential studies.  Other scientific approaches may be proposed.

The NCI recognizes that research in AIDS-Kaposi's sarcoma is

technically difficult to conduct because of the complexity of this

disease and the relatively limited availability of study subjects at

any single institution.  Thus, the NCI is encouraging the submission of

grant applications for research relevant to this PA in the context of

multi-institutional efforts under the interactive R01 mechanism (see



The aims of this initiative are two-fold: (1) to support innovative

correlative laboratory studies relevant to AIDS-Kaposi's Sarcoma

clinical trials and (2) to stimulate development of innovative AIDS-

Kaposi's sarcoma clinical studies with laboratory correlations so as to

foster the development of interactions between basic science

laboratories and clinicians performing these clinical trials.





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 the

Research Plan, 1-4 AND summarized in Section 5, Human Subjects.

Applicants 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 is defined as 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


If the required information is not contained within the application,

the application will be deferred until the information is provided.

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.


Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) and will be accepted at the deadlines as indicated in the

application kit for AIDS-related research (January 2, May 1, and

September 1).

Application kits are available at most institutional business offices

and may be obtained from the Office of Grants Inquiries, Division of

Research Grants, National Institutes of Health, Westwood Building, Room

449, Bethesda, MD 20892, telephone 301/496-7441.  The title and number

of the announcement must be typed in Section 2a on the face page of the


The completed original application and five legible copies must be sent

or delivered to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892


Applications will  be assigned on the basis of established Public

Health Service referral guidelines.

Applications will be reviewed for scientific and technical merit by

study sections of the Division of Research Grants, NIH, in accordance

with the standard NIH peer review procedures.  Following scientific-

technical review, the applications will receive a second-level review

by the appropriate national advisory council.


Applications will compete for available funds with all other approved

applications.  The following will be considered in making funding


o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement


Written and telephone inquiries are encouraged.  The opportunity to

clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Roy S. Wu

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

Dr. Giorgio Galetto

NIAID Program Director

National Institute of Allergy and Infectious Diseases

Control Data Building, Room 2C32

Bethesda, MD  20892

Telephone:  (301) 496-0700

FAX:  (301) 480-5703

Direct inquiries regarding fiscal matters to:

Ms. Carolyn Mason

Grants Management Specialist

National Cancer Institute

Executive Plaza South, Room 242

Bethesda, MD  20892

Telephone:  (301) 496-7800, ext. 59

FAX:  (301) 496-8601


This program is described in the Catalog of Federal Domestic Assistance

No. 93.395 Cancer Treatment Research No. 93.855, Immunology, Allergy,

and Immunologic Research, and No. 93.856, Microbiology and Infectious

for 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 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.


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