A randomized phase II study of paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer.

Abstract

TPS257 Background: The majority of patients diagnosed with ovarian cancer have advanced disease at the time of diagnosis, and are incurable with surgical therapy. Systemic chemotherapy, following initial cytoreductive surgery, has markedly improved the treatment of patients with advanced ovarian cancer. Standard first-line combination chemotherapy includes a taxane and a platinum agent. Further improvement in the first-line treatment of ovarian cancer will likely depend on the successful incorporation of novel, targeted agents into therapy. Several angiogenesis inhibitors have shown activity against refractory ovarian cancer. Sorafenib efficiently blocks the VEGF receptor and demonstrates antitumor activity in murine xenografts using a human ovarian cancer line (SKOV3). This randomized phase II study compares the efficacy and toxicity of a standard paclitaxel/carboplatin regimen, either alone or with the addition of sorafenib, in the first-line treatment of patients with stage III/IV ovarian cancer following cytoreductive surgery. Randomization of 120 patients will allow detection of an improvement in 2 yr PFS from 45% to 67% (α=.10). Methods: Eligibility: All patients must have previously untreated, histologically confirmed, stage III or IV epithelial ovarian carcinoma, with no residual tumor nodule > 3 cm, no involvement of the bowel (i.e. invasion into bowel wall) and no intestinal obstruction after surgical cytoreduction. Trial Design: Following recovery from cytoreductive surgery patients are randomized (1:1) to receive treatment with paclitaxel/carboplatin ± sorafenib. Regimen A: paclitaxel 175mg/m2, 1-3 hr infusion, day 1; carboplatin AUC=6.0 IV day 1; sorafenib 400 mg bid orally, days 1-21. Regimen B: paclitaxel/carboplatin (same doses as Regimen A). Cycles are repeated every 21 days. Patients are reevaluated every 6 weeks; responding/stable patients continue treatment for 6 cycles. After 6 cycles, responding patients on Regimen B continue single agent sorafenib to complete a 12 month course. Current Enrollment: 55 of 120 patients are currently enrolled. No significant financial relationships to disclose.