Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

Background: Sorafenib is an inhibitor of wild-type and mutant proto-oncogene BRaf (B-Raf) and proto-oncogene c-Raf (c-Raf) kinase isoforms in vitro, but it also inhibits mitogen-activated protein kinase (p38), proto-oncogene c-kit (c-kit), vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor (PDGFR)-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf. Bevacizumab is a humanized immunoglobulin G 1 (IgG1) monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (vascular endothelial growth factor (VEGF), or VEGF-A) with high affinity (kd = 1.1nM). Phase I trial of sorafenib and bevacizumab administered concurrently showed activity of the combination in patients with refractory ovarian cancer. Objectives: Determine the activity and tolerability of the combination bevacizumab and sorafenib in patients with refractory or recurrent epithelial ovarian, fallopian, or peritoneal cancer in patients who are bevacizumab-naive or bevacizumab-resistant. Eligibility: Adults with histologically documented refractory or recurrent epithelial ovarian, fallopian, or peritoneal cancer. Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks. Patients must have an Eastern Cooperative Oncology Group (ECOG) of 1 or less. Patients must have disease that is amenable to biopsy. Patients must have not been previously treated with bevacizumab or must have progressed on prior bevacizumab-based therapy. Design: Patients will be stratified on entrance to the trial based on their previous exposure to bevacizumab to either strata A (bevacizumab-naive patients) or strata B (patients previously treated with bevacizumab). Patients will receive oral sorafenib 200 mg twice daily 5 out of 7 days each week and intravenous bevacizumab 5 mg/kg every two weeks. Tumor biopsies will be obtained from patients before treatment and six weeks into therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fludeoxyglucose 18F-positron emission tomography (FDG-PET) will be obtained from patients before treatment, on day 3 of treatment, and six weeks into therapy. Patients will be evaluated for response every 8 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Approximately 74 patients will be needed to achieve the objectives of the trial.