The Chemoprevention Investigational Studies Branch of the Division of Cancer Prevention and Control at the National Cancer Institute has developed a program to identify and develop for human drugs which will prevent or suppress the development of cancer. This program includes the development of Phase II clinical trials supported by the MA mechanism. As part of this program, the Chemoprevention Investigational Studies Branch is also seeking to develop and validate intermediate endpoint biomarkers of cancer, i.e., precancerous biological and/or molecular changes in target epithelium that correlate with cancer risk and that can be modulated with a chemopreventive agent. Such intermediate endpoint biomarkers will significantly shorten the time required for clinical efficacy evaluation of promising chemopreventive agents. Intermediate endpoint biomarkers are classified as histological (dysplasia or a precancerous lesion), proliferative (labeling index, proliferation specific antigens, S-phase fraction by flow cytometry), differentiation, blood group antigens), loss of differentiation antigens) and genetic (aneuploidy and other chromosomal aberrations, activated oncogenes, loss of heterozygosity of tumor suppressor genes). Phase II clinical trials will be divided into two parts. Part A will be concerned with determination of dose and dosing regimens. Part B will involve a randomized, blinded trial in a small group of subjects the endpoint of which will be, at a minimum, one or more intermediate endpoint biomarkers showing a measurable effect of the agent versus the placebo.
