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.
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.
|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 Estimated 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|
|Soumerai, Jacob D; Zelenetz, Andrew D; Moskowitz, Craig H et al. (2017) The PARP Inhibitor Veliparib Can Be Safely Added to Bendamustine and Rituximab and Has Preliminary Evidence of Activity in B-Cell Lymphoma. Clin Cancer Res 23:4119-4126|
|Niu, Jing; Scheuerell, Christie; Mehrotra, Shailly et al. (2017) Parent-Metabolite Pharmacokinetic Modeling and Pharmacodynamics of Veliparib (ABT-888), a PARP Inhibitor, in Patients With BRCA 1/2-Mutated Cancer or PARP-Sensitive Tumor Types. J Clin Pharmacol 57:977-987|
|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|
Showing the most recent 10 out of 39 publications