Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Daniel D Von HoffJohanna C Bendell

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 r...Continue Reading

References

Jul 12, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y K OngE H Tan
Aug 12, 2003·Oncogene·Bruce F Israel, Shannon C Kenney
Mar 29, 2005·The Oncologist·Edvardas KaminskasRichard Pazdur
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Oct 11, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kim AppletonRobert Brown
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 18, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guillermo Garcia-ManeroBarry Skikne
Oct 1, 2009·Epigenomics·Marina BibikovaKevin L Gunderson
Dec 1, 2011·Epigenomics·Sarah DedeurwaerderFrançois Fuks
Oct 29, 2013·Oncotarget·John WrangleStephen B Baylin

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