Results from early phase clinical trials have been the cornerstone upon which Phase 2 and 3 efforts are constructed, and upon which scientific inference relative to the biological basis for drug action is imputed. This new era in drug development-an era of molecularly targeted treatments-represents a paradigm shift in how early phase studies are considered relative to the "conventional" approach of treating without consideration to underlying tumor genomics, biology and immunology. Translational endpoints, including levels of target expression, engagement, and modulation of downstream effectors are being assessed as early as possible, and increasing emphasis is being placed on early patient selection, utilizing novel biomarker assays and molecular characterization to identify patients most likely to respond. The ultimate purpose of the NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN) is to define better approaches for the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly and find appropriate biomarkers to select patients most likely to respond to specific agents. The goals of the ET-CTN cannot be achieved by any single investigator or institution and will require collaborative, diverse, and committed members with complementary expertise. To assemble the synergistic expertise required to assist ET-CTN in reaching its goals, a comprehensive team has been formed to perform clinical and translational research in this new era of drug development. This team aims to 1) conduct carefully-controlled early clinical trials of novel anticancer agents and combinations;2) recruit at least 12% underserved/special populations;3) study the clinical pharmacology, pharmacokinetics, pharmacodynamics, and pharmacogenomics of novel agents, and where appropriate, incorporate noninvasive imaging tools;and 4) utilize biomarker assays and advanced molecular characterization tools to identify molecular factors associated with treatment response and resistance. The members of this team have a unique set of complementary expertise and a similar philosophy regarding collaborative research and mentorship of the next generation of cancer investigators. This partnership has been termed the Vanderbilt-lngram, Karmanos, TGen Research Institute, Yale - Early Cancer Therapeutics Consortium (ViKTriY - ECTC). This ViKTriY team is committed to utilizing their areas of expertise and maximizing their collaborative relationships with the ultimate mission of improving outcomes for patients with cancer.
This application describes a multidisciplinary team that will conduct early phase cancer clinical trials and correlative translational studies. This work will provide the dose, schedule, and early evidence of activity to guide later phase trials, molecularly characterize tumors, and find appropriate biomarkers for better patient selection for drug response to ultimately improve outcomes for cancer patients.
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