A -- PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS AND THEIR MODULATION BY CHEMOPREVENTIVE AGENTS

Notice Date

May 7, 2001

Contracting Office

National Cancer Institute, Research Contracts Branch, PCPSS, Executive Plaza South, Room 635, Bethesda, Md 20892

ZIP Code

20892

Solicitation Number

RFP/MAO-N01-CN-15012-72

Response Due

June 28, 2001

Point of Contact

Jacqueline Ballard, Contracting Officer 301-435-3795

E-Mail Address

Jacqueline Ballard (ballardj@mail.nih.gov)

Description

The National Cancer Institute, Division of Cancer Prevention, (DCP) Chemoprevention Agent Development Research Group (CADRG) is interested in conducting animal cancer model studies of biomarkers and intermediate endpoints that might be used in human clinical trials in order to examine in detail the biomarker modulating effects of selected chemopreventive compounds. In addition the studies will improve biomarker sensitivity, specificity, assay methodology, and sample handling. The emphasis will be on efficient studies aimed at providing more quantitative, and more validated intermediate endpoints for future human clinical trials. Intermediate endpoints or biomarkers that are directly associated with the evolution of neoplasia, and that develop with much higher frequency in abnormal cells of susceptible individuals than do the actual tumors, will make it possible in the future to carry out many studies on fewer subjects for shorter durations. If such biomarkers were found to be modified by a particular intervention regimen in preclinical studies, a rationale would be provided for carrying out clinical studies. The application of biological markers to clinical cancer prevention trials carries great promise in relation to ultimate cancer prevention. When neoplasia itself is used as an end point in studies of this type, a very large number of subjects tested for long durations are often required. The results of these in vivo experiments will be used to select promising intermediate endpoints for Phase II human studies whose objectives are to study the modulation of a selected biomarker in response to a chemopreventive agent. These relevant preclinical studies will be used to help achieve one of the major goals of the chemoprevention program which is the timely evaluation of chemopreventive agents in clinical trials. A number of chemical compounds and/or dietary components have been shown to inhibit carcinogenesis in animal models, in vitro systems, and to be associated with cancer reduction in epidemiological studies. Results from animal studies suggest that a number of compounds and/or dietary components may affect several stages of carcinogenesis. A variety of excellent biomarkers are now available. Examples include reversal of abnormal cytology, ornithine decarboxylase activity, prostaglandin synthetase inhibition, DNA ploidy alterations, changes in cellular proliferation (e.g., tritiated thymidine or BrdU labeling indices, decreases in PCNA or Ki-67 antigens, or histology), and oncogene suppression tests. The development and utilization of sensitive and accurate intermediate endpoints should enhance the ability to design effective human Phase II clinical trials. This RFP will involve multiple workstatements (Nos. 53-61). Certain study design characteristics apply to the specific Workstatements under this RFP. Most of the requirements for the Workstatement study design will be detailed in the specific workstatement. Each workstatement will have a specific period of performance. The workstatements are: WS #53: Evaluation of farnesylation-related chemopreventive agents to modulate selected surrogate biomarkers and to reduce or retard cancer incidence in a preclinical hamster model of pancreatic carcinogenesis; WS #54: Evaluation of lipoxygenase-related chemopreventive agents to modulate surrogate biomarkers and to reduce or retard cancer incidence in a preclinical hamster model of pancreatic cancinogenesis; WS #55: Examination of multiple biomarker endpoints in rat mammary tissues and tumors, mouse bladders, and rat tongue tumors; WS #56: Efficacy Testing of Selected Chemopreventive Agents in the TRAMP Prostate Cancer Model; WS #57: Altered Genes Expression in Mouse Bladder Epithelial and Mouse Bladder Tumors and Rat Esophageal Epithelial and Rat Esophageal Tumors: Modulation of gene expression by known chemopreventive agents; WS #58: Chemopreventive studies and modulation of intermediate endpoints in a hormonal mediated model of mouse prostate cancer; WS #59: Use of a smoke induced models of lung carcinogenesis for screening of chemopreventive agents and potential use of DNA adducts in this model; WS #60: Effect of chemopreventive agents on the incidence of colorectal cancer in the APC/MLH1+/- mutuant mouse; and WS #61: Chemopreventive screening employing a rat surgical model for esophageal metaplasia and adenocarconinoma. This RFP/MAO will be available electronically to all the current Master Agreement Holders. Those interested in obtaining a copy of this RFP should send their e-mail address to Jacqueline Ballard at ballardj@mail.nih.gov and a copy of the RFP will be forwarded electronically. Proposals will only be considered from offerors in this Pool. AWARDS WILL ONLY BE MADE TO A MASTER AGREEMENT HOLDER IN THE PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS AND THEIR MODULATION BY CHEMOPREVENTIVE AGENTS POOL. For those who are not currently in the Master Agreement Pool who wish to be considered for inclusion should consult the Research Contracts Branch website at http://rcb.nci.nih.gov. under "Current Requests for Proposals" and refer to RFP-MA-N01-CN-85052-72. The duration of the existing Master Agreement pool is through December 29, 2002. The annual due date for proposals is February 1 of each year for those interested in being included in the projected annual review. It is the offeror's responsibility to monitor the above internet site for the release of this solicitation and amendment, if any. Potential offerors will be responsible for downloading their own copy of the solicitation and amendment. (Hard copies will be available only upon individual request). It is anticipated the RFP-N01-CN-15012-72, will be available by May 25, 2001. In order to be considered for award, all offerors shall be current holders of a "Preclinical Evaluation of Intermediate Endpoints and their Modulation by Chemopreventive Agents" Master Agreement and shall be members of this pool as of the May, 2001 release date of this RFP. All questions should be directed, via facsimile or e-mail to Jacqueline Ballard, Contracting Officer, Prevention and Control Population Sciences Contracts Section, Research Contracts Branch, National Cancer Institute, NIH, Executive Plaza South, Room 635, 6120 Executive Boulevard, MSC 7226 Rockville, Md. 20852. Phone: 301-435-3795; Fax: 301-402-8579; Email address: ballardj@mail.nih.gov. The North American Industry Classification System (NAICS) code is 54171. All request should reference the RFP No. N01-CN-15012-72. No collect calls will be accepted. Number Note 26 -- Based upon market research, the Government is not using the policies contained in Part 12, Acquisition of Commercial Items, in its solicitation for the described supplies or services. However, interested persons may identify to the contracting officer their interest and capability to satisfy the Government's requirement with a commercial item within 15 days of this notice.

Web Link

http://rcb.nci.nih.gov/ncics/rfps_published.asp (http://rcb.nci.nih.gov/ncics/rfps_published.asp)

Record

Loren Data Corp. 20010509/ASOL006.HTM (W-127 SN50L3K9)