Early Clinical Trials of New Anti-Cancer Agents

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Roughly 500 anti-cancer agents will be available for development within the next decade. The Phase I community will face significant challenges making swift and accurate go/no go drug developmentdecisions, due to limited resourcesfor continued clinical development as well as potentially unique profiles that the clinical drug candidates may unfold. It is important to be proactive, anticipating many of the challenges. Maximizing the knowledge base and combining resources to assist in overcoming many of these challenges will be a key component of continued success. Karmanos Cancer Institute (KCI) and University of Maryland Marlene & Stewart Greenebaum Cancer Center(UMGCC)jointly are submitting this proposal to maximize our strengths as a Phase I Consortium. The combined expertise of both institutions define us asthought eaders in pharmacokinetics (PK), pharmacodynamics (PD), imaging and biostatistics, all necessary components of an efficient and effective phase I program. Both institutions have recognized the greater need for understanding tumor-related targeted drug effects. Drs. LoRusso (KCI Principal Investigator) and Sausville (UMGCC Principal Investigator) have both involved exploration of PD effects of several different classes of agents. Dr. Sausville has developed a PD translational research laboratory at UMGCCto help further develop select PD endpoints for implementation in the clinical trials to be pursued by thisconsortium. The combined expertise of Drs. LoRusso and Sausville lend collectively at least 40 years experience in preclinical and clinical cancer drug development. Their efforts have led to the development of several commercially available or recently filed agents, including Velcade¿, Ontak¿, capecitabine, zoledronic acid, gefitinib, lapatanib, and ixabepilone, to name a few. Their programs have recognized that patient resources are valuable and limited, and have had significant success developing and evaluating novel trial designs to minimize patients treated at ineffective doses. The locations of both institutions lend themselves to service inner city populations with large women and minority bases, offering the potential for special population studies. Dr. Shields, our collaborator at KCI, has been a thought leader in PET imaging, with several tracers, including FDG and FLT, to his portfolio. This imaging oriented capacity is yet an additional unique feature available to his consortium. With the continued growth and expansion of both programs, we feel this collaboration will be well positioned for the continued development of novel agents offered through the Cancer Treatment Evaluation Program at the National Cancer Institute.