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

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1CA186690-05
Application #
9699368
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Ivy, S Percy
Project Start
2014-03-25
Project End
2020-02-28
Budget Start
2019-03-01
Budget End
2020-02-28
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15260
Appleman, Leonard J; Maranchie, Jodi K (2018) Systemic therapy following metastasectomy for renal cell carcinoma: Using insights from other clinical settings to address unanswered questions. Urol Oncol 36:17-22
Beumer, Jan H; Chu, Edward; Allegra, Carmen et al. (2018) Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5-Fluorouracil Therapy. Clin Pharmacol Ther :
Beumer, Jan H; Inker, Lesley A; Levey, Andrew S (2018) Improving Carboplatin Dosing Based on EstimatedĀ GFR. Am J Kidney Dis 71:163-165
Singh, Renu; Mehrotra, Shailly; Gopalakrishnan, Mathangi et al. (2018) Population pharmacokinetics and exposure-response assessment of veliparib co-administered with temozolomide in patients with myeloid leukemias. Cancer Chemother Pharmacol :
Benoist, Guillemette E; van der Meulen, Eric; van Oort, Inge M et al. (2018) Development and Validation of a Bioanalytical Method to Quantitate Enzalutamide and its Active Metabolite N-Desmethylenzalutamide in Human Plasma: Application to Clinical Management of Patients With Metastatic Castration-Resistant Prostate Cancer. Ther Drug Monit 40:222-229
Vendetti, Frank P; Karukonda, Pooja; Clump, David A et al. (2018) ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation. J Clin Invest 128:3926-3940
Bakkenist, Christopher J; Lee, James J; Schmitz, John C (2018) ATM Is Required for the Repair of Oxaliplatin-Induced DNA Damage in Colorectal Cancer. Clin Colorectal Cancer 17:255-257
Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer et al. (2017) Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation. Sci Rep 7:41892
Zhang, Yaping; Hu, Kaiqiang; Beumer, Jan H et al. (2017) RAD-ADAPT: Software for modelling clonogenic assay data in radiation biology. DNA Repair (Amst) 52:24-30
Matsumoto, Julia; Kiesel, Brian F; Parise, Robert A et al. (2017) LC-MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma. J Pharm Biomed Anal 146:154-160

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