Technical support products include agent background, rationale, chemistry, and testing documents for use in decision making and in planning clinical development strategies by the DCP Agent Development Committee; by the Chemopreventive Agent Development Research Group and other DCP Research Groups; by the Rapid Access to Preventive Intervention Development (RAPID) Program; by regulatory support, clinical trial monitoring, and repository acquisition, formulation, and distribution personnel under contract to the DCP; and, as appropriate, by investigators conducting the preclinical studies and clinical trials; by DCP program staff for analysis and planning; by NCI program review committees established following recommendations of the NCI Board of Scientific Advisors; and by other NCI staff, officials of other government agencies, and other scientists (e.g., at universities, research institutes, medical centers, pharmaceutical and other private sector collaborator sites, etc.). Sophisticated, comprehensive and multi-disciplinary technical resources are required because currently the DCP senior scientists scrutinize and prioritize hundreds of candidate agents yearly for initial preclinical evaluation, continually evaluate dozens of agents in clinical development tracks at milestone decision points for further development with the objective of qualifying agents for INDs and early clinical trials, and oversee a portfolio of advanced clinical trials of potential cancer preventive agents. Additionally, advances in -omic technologies, molecular modeling, and bio-informatics related to agent identification, optimization, development, and qualification for clinical testing are increasing information management requirements in order to make informed decisions and strategic planning.The DCP has established and implemented a clearly defined integrated plan for evaluating chemopreventive agents. The plan includes: (1) identifying potential cancer preventive agents from epidemiological observations, experimental carcinogenesis and pharmaceutical literature, applications to the RAPID program, interactions with private industry and academic investigators, and/or theoretical considerations, (2) qualifying agents for potential further development through in vitro and in vivo screening assays, (3) conducting efficacy, pharmacology, intermediate endpoint, and toxicity studies of candidate agents in animal models, and (4) preparing supplies of cGMP investigational agents and conducting phase 1 pharmacokinetic and safety trials, phase 2 efficacy and intermediate endpoint trials, and phase 3 efficacy endpoint trials of the most promising agents. Detailed criteria are delineated for classifying the quantity and quality of information that currently exists on any chemopreventive agent and thus defining what additional information and investigations are required to qualify the experimental use of an agent in intervention trials of human cancer. Thus, the primary purpose of this project shall be to provide research, technical support, and analysis to assist in evaluating ongoing and proposed activities.
