Quick-trials for novel cancer therapies: exploratory grants.

Continuing progress in basic cancer research and drug development has led to discoveries of new agents or approaches for molecular targeting in novel cancer therapies. These new agents or approaches suppress tumor growth through multiple mechanisms such as cell cycle control, activation of tumor suppressor genes, essential signal pathway blockage, tumor vaccines, tumor microenvironment modification, etc. Rapid translation of these exciting discoveries into clinical practice requires timely support to accommodate the special needs of novel cancer therapy development. This Program Announcement (PAr is intended to provide investigators with rapid access to support for pilot, Phase I, and Phase II cancer clinical trials as well as support for patient monitoring and laboratory studies linked to a cancer clinical trial. Phase III trials are not excluded but such trials generally require greater resources and duration than available from an R21 award. Applications that do not propose a cancer clinical trial or patient monitoring or laboratory studies linked to a cancer clinical trial may be returned to applicants without being reviewed. The focus of this Quick-Trial PA is on translational research in new agent development to ensure the timely exploitation of new cancer therapeutic approaches including the development of new cancer prevention agents. This PA is aimed at providing a new approach in the grant application process by offering a rapid turnaround from application submission to funding. Features of this initiative include a modular grant application and award process, inclusion of the clinical protocol within the grant application, and an accelerated peer review with the goal of issuing new awards within six 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 and to insure proper peer review of the application. In addition, Quick-Trial applications do not require extensive preliminary data in the grant application and support exploratory translational and clinical research studies involving cancer prevention, chemotherapy and rapid development and application of novel clinical cancer therapies including image guided therapeutic procedures. Investigators may apply for a maximum of two years of funding support using the exploratory or developmental (R21) grant mechanism for up to $250,000 direct costs per year.

Advances in the understanding of molecular cancer genetics, basic cancer biology, and the development of powerful technologies such as microarray, proteomics and bioinformatics have led to the identification of many new molecular targets and pathways in cancer cells. These discoveries have created new frontiers for novel molecular cancer prevention and treatment leading to the development of molecular medicine in cancer therapy. In addition, these novel targets and pathways have presented excellent translational research opportunities for revolutionizing cancer drug development and bringing more effective molecular cancer therapies and cancer prevention strategies into clinical practice.

Novel approaches or agents for inhibiting tumor growth either directly or by impacting the tumor microenvironment are ready to be tested in the clinic with new tools and laboratory analyses that allow investigators to ascertain how specific targets are affected by therapy. These agents include new classes of cytotoxic agents, agents or approaches that act via immune-stimulatory effects, agents that stimulate apoptosis, inhibit angiogenesis and metastasis or alter tumor cell signaling pathways, and agents targeted specifically to novel cancer cell targets. New clinical therapeutic trials may employ drags/agents, biologics, radiation, heat, or surgery used as single agents/modalities or in combination for the treatment of early and advanced disease. In addition, clinical trials of therapies for cancer treatment, including but not limited to herbal therapies, dietary supplements, bioactive food components, or unconventional pharmacological and biological interventions (e.g. antineophstons, Coley's toxin, enzyme therapies, etc.) will be considered. Another relevant area of investigation is the use of anatomical and molecular image guidance for targeted treatment with ablative techniques or delivery of chemotherapeutic agents. At present, there are few funding mechanisms targeted to stimulate the translation of promising and potentially relevant advances in new prevention or therapeutic agent 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 traditional health benefit programs. Nonetheless, these early studies tend to fare poorly in competition for conventional grant support precisely because they are preliminary and cannot 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, 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 tested in more than one or two diseases.

This PA will continue to support scientific, technological, clinical and logistical needs in novel cancer therapy development. In addition, this PA will complement the Rapid Access to Intervention Development (RAID) program http://dtp.nci. nih.gov/docs/raid/raid_index.html by providing an 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.

This PA will use the NIH exploratory/development (R21) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. The applicant may request a project period of up to 2 years with direct costs limited to $250,000 per year.

This PA uses just-in-time concepts, it also uses the modular budgeting format (see http://grants. nih.gov/grants/funding/modular/modular.htm). This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/ NIHGPS_Part2.htm.

Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for federal grants or cooperative agreements. The D&B number can be obtained by calling 866-705-5711 or through the web site at http:// www.dunandbradstreet.com/. The D&B number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/ phs398.html in an interactive format. For further assistance, contact GrantsInfo, 301-435-0714, e-mail: [e-mail]. The title and number of this PA must be typed on line 2 of the face page of the application form and the YES box must be checked.

Because Quick-Trial applications will propose cancer clinical trials or patient monitoring or laboratory studies linked to a cancer clinical trial, applicants are reminded to properly complete item e (Humans Subjects Research) of the Research Plan. This is described in PHS 398. As applicable, the Human Subjects Research portion of the Research Plan includes, but is not limited to, a Data and Safety Monitoring Plan, Women, Minority, and Children Inclusion sections, and a Targeted/Planned Enrollment Table.

Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to: Center for Scientific Review, National Institutes of Health, 6701 Rockledge Drive, Room 1040, MSC 7710, Bethesda, MD 20892-7710 USA; Bethesda, MD 20817 (for express/courier service).

The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an unfunded version of an application already reviewed, but such application must include an introduction addressing the previous critique.

Contact: Roy Wu, Clinical Grants and Contracts Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer institute (NCI), 6130 Executive Boulevard, EPN Room 7009, Bethesda, MD 20892-7432 USA; Rockyville, MD 20852 (for express/courier service), 301-496-8866, fax: [phone], e-mail:[e-mail]

Reference: PA No. PAR-04-155