A phase i trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study

Lisa M. Landrum, William E. Brady, Deborah K. Armstrong, Kathleen N. Moore, Paul A. Disilvestro, David M. O'Malley, Meaghan E. Tenney, Peter G. Rose, Paula M. Fracasso

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of veliparib combined with PLD and carboplatin (CD) in patients with recurrent, platinum-sensitive epithelial ovarian cancer. To determine the tolerability at the MTD combined with bevacizumab. Methods Patients received PLD (30 mg/m2, IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 1-7 (intermittent) or days 1-28 (continuous). Standard 3 + 3 design was used in the dose escalation phase with DLTs based on the first cycle. Once the MTDs were determined, cohorts of 6 patients were enrolled to each regimen with bevacizumab (10 mg/kg on days 1 and 15) to assess feasibility. DLTs were based on the first 4 cycles of treatment in the bevacizumab cohorts. Results In the dose-escalation phase, 27 patients were treated at 3 dose levels with DLTs noted in 6 patients including grade 4 thrombocytopenia (n = 4), and prolonged neutropenia > 7 days (n = 3). At the MTD of veliparib (80 mg p.o. b.i.d. for both dosing arms), myelosuppression was the DLT. At MTD, 12 additional patients were treated with bevacizumab with 9 patients experiencing DLTs including grade 4 thrombocytopenia (n = 4), prolonged neutropenia > 7 days (n = 1), grade 3 hypertension (n = 5), and grade 5 sepsis (n = 1). Conclusions The MTD of veliparib combined with CD is 80 mg p.o. b.i.d. in women with recurrent, platinum-sensitive ovarian cancer. With bevacizumab, DLTs were noted in 9 out of 12 patients. Lower doses of veliparib will need to be considered when given in combination with platinum-based therapies.

Original languageEnglish (US)
Pages (from-to)204-209
Number of pages6
JournalGynecologic oncology
Volume140
Issue number2
DOIs
StatePublished - 2016

Keywords

  • PARP inhibitors
  • Thrombocytopenia
  • VEGF inhibitors

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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