Task I: Single-dose Pharmacokinetic Study The Contractor shall develop a single-dose, phase 1 clinical protocol for p-XSC to evaluate the parameters of drug absorption, plasma concentration- time profiles, distribution (in relevant tissues, where feasible), excretion, and toxicity. Task II: Multiple-dose Safety and Pharmacokinetic Study The Contractor shall develop a multiple-dose safety and pharmacokinetic phase 1 clinical protocol for the chemopreventive agent to evaluate the parameters of safety and toxicity and of steady-state pharmacokinetics. In addition, investigations of pharmacological and/or cancer surrogate endpoint biomarker modulation may be undertaken, e.g. modulation of apoptosis, PGE2, GSH-Px, or urinary adducts. Protocol activation for Task I and Task II will occur following IRB and FDA approval and the receipt of all chemopreventive drug(s) from the NCI by the Contractor. The Contractor shall submit the protocol to NCI DCPC Protocol Safety and Review Committee for review and comment, address all issues raised in the NCI review, and submit a finalized protocol for IRB approval. The Contractor shall prepare all materials necessary for FDA approval. The NCI will submit the protocol to the FDA and will hod the IND.
