Phase II study of sorafenib (BAY 43–9006) in combination with gemcitabine in recurrent epithelial ovarian cancer: A PMH phase II consortium trial

Abstract

5084 Background: Sorafenib (BAY 43–9006; SOR) is a novel multi-targeted kinase inhibitor that targets the RAF/MEK/ERK signaling pathway, vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor and flt-3. VEGFR is over-expressed in human ovarian tumors and this is associated with poor prognosis. Gemcitabine (GEM) is known to have single-agent activity in recurrent ovarian cancer (OC). A recent phase I study of GEM/SOR has demonstrated manageable toxicity and some objective responses in recurrent OC patients. We have designed a phase II trial to evaluate the efficacy of this novel combination in patients with recurrent OC. Methods: A two-stage, phase II clinical trial is underway for women with recurrent or refractory OC. Eligible patients may have received up to 2 prior lines of chemotherapy following recurrence, but must be GEM-naive. The treatment consists of SOR, 400mg PO bid continuously, in combination with GEM, IV weekly, 1000 mg/m2. Cycle 1 is an extended cycle of 7 weeks of GEM followed by a 1-week break. GEM is administered weekly for the first 3 weeks of each subsequent 4-week cycle. The primary endpoint is objective response rate, with response evaluated every 8 weeks. Results: 26 patients have been enrolled at 3 centers. 84 cycles have been administered (median 3; range 1–10). Median age was 57 (range: 37–77). 42% were ECOG PS 0 and 58% were PS 1. Of 18 patients evaluable for objective response, 1 patient had a confirmed PR by RECIST criteria and 5 patients had a confirmed PR by CA-125 criteria, yielding a combined RR of 33% in evaluable patients (RR by ITT = 23%). An additional 10 patients had SD. The median time to progression is 7.6 months (95% CI: 5.6-NA). 7 patients are inevaluable for objective response due to the following in cycle 1: withdrawal of consent (3), toxicity (2), and clinical PD (2). 1 patient on-study is yet to have a response evaluation. Grade 3 or 4 toxicities seen in more than 2 patients include: lymphopenia (8), thrombocytopenia (6), hypertension (3), hand-foot syndrome (3), pain (3), neutropenia (3) and hypokalemia (3). Conclusions: The preliminary results show encouraging activity with tolerable toxicity. This trial continues to accrue into a second stage. No significant financial relationships to disclose.