Recent advances in science and biotechnology have led to an explosion of data from the plethora of rapidly developing high throughput analyses. While these advances have led to major improvements in the therapy of several refractory malignancies, most advanced cancers remain incurable. The Southwest Early Clinical Trials (SECT) Consortium consists of University of Texas MD Anderson Cancer Center and University of Colorado Comprehensive Cancer Center, and is strategically and geographically placed to lead, collaborate on and execute phase I clinical trials in the NCI Experimental Therapeutics-Clinical Trials Network in broad patient populations, including in several underserved regions. Specifically, we propose to: 1. Study, in an efficient and collaborative manner, the safety and clinical activity of new agents or hypothesis-driven novel combinations. 2. Molecularly profile patients (host tissues) and their malignancies to optimize selection of potentially relevant therapy for each patient, based on identified molecular aberrations, where appropriate. 3. Develop clinically relevant pharmacodynamic markers of response. 4. Mentor junior faculty, trainees, and research personnel, as applicable, in the leadership, conduct, analysis, and reporting of ET-CTN and other clinical trials. 5. Provide scientific and administrative leadership within ET-CTN, including active participation in project teams, research design and protocol development, authorship/co-authorship of Network group publications, and participation in scientific, administrative, or ad hoc committees, as well as participation in the NCI Central IRBs and attendance at ET-CTN and IDSC meetings. In addition to established proficiency in clinical trial accrual, pharmacokinetics, and pharmacodynamic assessment, the SECT Institutions have an unparalleled combination of resources that include access to large patient populations with extensively genotyped tumors, established biorepositories, state of the art clinical genomics capabilities, and expert bioinformatics. Led by three experienced principle investigators with complementary skills, the SECT consortium is poised to execute a new paradigm for early experimental therapeutic clinical trials, with the goals to validate the right pathways, target thee pathways with the right drugs, and test these drugs in the right patients.
Early oncology clinical trials have traditionally focused on defining the maximum tolerated dose for phase II development. Recent development of novel targeted agents demand a different approach that includes: 1) testing in a molecularly profiled population;2) evaluation f intermediate biologic endpoints;and 3) determination of the optimal biologic dose for Phase II studies.