For more than 40 years, the NCI has supported a clinical trials infrastructure program to conduct early phase clinical trials across the US. As par of its efforts to enhance, facilitate, and expedite the process of early-phase drug development, the NCI created the NCI Experimental Therapeutics Program (NExT), which represents a joint early therapeutics development program between NCI intramural and extramural teams/institutions to prioritize a pipeline of NCI-driven targeted therapeutics. The NCI has now developed a comprehensive plan to transform the NCI-sponsored cooperative experimental therapeutics clinical trials program from a series of separate institutions conducting early-phase cancer treatment trials to a new consolidated, integrated Program, referred to as the NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN). The University of Pittsburgh Cancer Institute (UPC) has been an NCI-designated comprehensive cancer center since 1990, and the UPCI has been involved in the NCI-U01 Phase I Early Drug Development Program since 1999. We now propose to be part of the new NCI ET-CTN as a Lead Academic Organization with the following specific aims: (1) to conduct early-phase experimental therapeutic clinical trials using single or combinations of novel agents from the NCI-CTP IND portfolio;(2) to participate on investigational agent-specific Project Teams to define the drug development plan;(3) to investigate the PK/PD aspects of the experimental agents and establish potential relationships between dose, schedule, exposure, and biological/antitumor effect;(4) to develop statistically appropriate clinical trial designs, including integral and integrated biomarker trials, accelerated titration, adaptive designs, and other design schemes;(5) to investigate special study populations with hepatic and/or renal dysfunction;(6) to evaluate data from related laboratory-based studies that assess drug-drug interactions;and (7) to evaluate translational endpoints in clinical trials of investigational agents.

Public Health Relevance

As a Lead Academic Organization of the NCI Experimental Therapeutics Clinical Trials Network, the UPCI plans to leverage its significant experience and leadership in early-phase clinical drug development and facilitate the early-phase clinical development of novel therapeutic agents and combinations that are of high priority to the NCI and the national interest. The long-term goal of this effort is to guide future disease specific clinical trials tha may have the potential to change the standard of cancer care in the US and worldwide.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZCA1-RTRB-E (J1))
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Ivy, S Percy
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Kunos, Charles A; Chu, Edward; Beumer, Jan H et al. (2016) Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies. Cancer Chemother Pharmacol :
Beumer, Jan H; Tawbi, Hussein; Ivy, S Percy (2016) Reply to V. Launay-Vacher, T. Shimokata et al, and C. Porta et al. J Clin Oncol 34:2430-1
Gojo, Ivana; Beumer, Jan H; Pratz, Keith W et al. (2016) A phase 1 study of the PARP inhibitor veliparib in combination with temozolomide in acute myeloid leukemia. Clin Cancer Res :
Lee, James J; Beumer, Jan H; Chu, Edward (2016) Therapeutic drug monitoring of 5-fluorouracil. Cancer Chemother Pharmacol 78:447-64
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Villaruz, Liza C; Jones, Helen; Dacic, Sanja et al. (2016) ATM protein is deficient in over 40% of lung adenocarcinomas. Oncotarget :
Beumer, Jan H; Ding, Fei; Tawbi, Hussein et al. (2016) Effect of Renal Dysfunction on Toxicity in Three Decades of Cancer Therapy Evaluation Program-Sponsored Single-Agent Phase I Studies. J Clin Oncol 34:110-6
Ivy, S Percy; Beumer, Jan H (2015) Ovarian Cancer Survival and Chemotherapy Dosing, Body Mass Index, and Body Surface Area : Are We There Yet? JAMA Oncol 1:732-3

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