Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors
Year: 2018
Type: article
Study design: Clinical Trial
Abstract: Purpose: This large two-part, three-arm phase I study examined the safety and tolerability of CC-486 (an oral formulation of azacitidine, a hypomethylating agent) alone or in combination with the cytotoxic agents, carboplatin or nab-paclitaxel, in patients with advanced unresectable solid tumors. Patients and Methods: Part 1 (n = 57) was a dose escalation of CC-486 alone (arm C) or with carboplatin (arm A) or nab-paclitaxel (arm B). The primary endpoint was safety, MTD, and recommended part 2 dose (RP2D) of CC-486. In part 2 (n = 112), the primary endpoint was the safety and tolerability of CC-486 administered at the RP2D for each treatment arm, in tumor-specific expansion cohorts. Secondary endpoints included pharmacokinetics, pharmacodynamics, and antitumor activity of CC-486. Results: At pharmacologically active doses CC-486 in combination with carboplatin or nab-paclitaxel had a tolerable safety profile and no drug–drug interactions. The CC-486 RP2D was determined as 300 mg (every day, days 1–14/21) in combination with carboplatin (arm A) or as monotherapy (arm C); and 200 mg in the same dosing regimen in combination with nab-paclitaxel (arm B). Albeit limited by the small sample size, CC-486 monotherapy resulted in partial responses (three/eight) and stable disease (four/eight) in patients with nasopharyngeal cancer. Three of the stable disease responses lasted more than 150 days. Conclusions: CC-486 is well tolerated alone or in combination with carboplatin or nab-paclitaxel. Exploratory analyses suggest clinical activity of CC-486 monotherapy in nasopharyngeal cancer and provided the basis for an ongoing phase II clinical trial (ClinicalTrials.gov identifier: NCT02269943). Clin Cancer Res; 24(17); 4072–80. ©2018 AACR.
Source: Clinical Cancer Research
Authors: Daniel D. Von Hoff, Drew W. Rasco, Elisabeth I. Heath, Pamela N. Munster, Jan H.M. Schellens, Nicolas Isambert, Christophe Le Tourneau, Bert O'Neil, Ron H.J. Mathijssen, Jose A. Lopez-Martin, W. Jeff Edenfield, Miguel Martin, Patricia M. LoRusso, Gordon L. Bray, Jorge DiMartino, Aaron Nguyen, Kejian Liu, Eric Laille, Johanna C. Bendell
Institutions: Translational Genomics Research Institute, HonorHealth, South Texas Accelerated Research Therapeutics, Wayne State University, The Barbara Ann Karmanos Cancer Institute, University of California, San Francisco, The Netherlands Cancer Institute, Centre Georges François Leclerc, Inserm, Institut Curie, Indiana University Health, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Erasmus MC, Erasmus MC Cancer Institute, Research Institute Hospital 12 de Octubre, University of South Carolina, Greenville Memorial Hospital, Universidad Complutense de Madrid, Hospital General Universitario Gregorio Marañón, Celgene (United States), Sarah Cannon, Tennessee Oncology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Cancer Institute
Award: CANCER CENTER SUPPORT GRANT
OpenAlex ID: W2803889088