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 JNRG Oncology/Gynecologic Oncology Group study

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/m(2), IV) and carboplatin (AUC 5, IV) on day 1 with veliparib on days 17 (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 MID, 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 MTh 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. (C) 2015 Elsevier Inc. All rights reserved.