Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

Summary

Background: * Sorafenib and bevacizumab are anti-cancer drugs that work by targeting the blood vessels that allow tumors to grow. Using the two drugs together may more effectively block the formation of blood vessels that feed tumors. * Sorafenib and bevacizumab both are approved by the Food and Drug Administration for use in other cancers but have not ovarian cancer. In a preliminary trial of this drug combination, however, tumors in 6 of 14 patients with ovarian cancer shrank. Objectives: * To determine the safety and activity of the combination of sorafenib and bevacizumab for treating patients with ovarian, fallopian and peritoneal cancer. * To determine how sorafenib and bevacizumab may affect the cancer by measuring amounts of different proteins in small biopsy samples of tumor taken before starting treatment and after 6 weeks. Eligibility: * Females 18 years of age and older with ovarian, fallopian, or peritoneal cancer whose disease has not responded to standard treatment or for which no standard treatment is available. * Patients must have not been previously treated with bevacizumab or must have had their disease worsen while taking bevacizumab-based therapy. Design: * Patients take 200 mg of sorafenib by mouth twice a day Monday through Friday each week and 5 mg/kg of bevacizumab through a vein every 2 weeks. * Tumor biopsies and imaging scans (magnetic resonance imaging (MRI) and positron emission tomography (PET) are done before treatment, 3 days after beginning treatment, and 6 weeks into therapy. * Computed tomography (CT) or other imaging tests are done every 8 weeks to evaluate response to treatment. * History, physical examinations, blood and urine tests are done periodically during treatment for health checks and research purposes. * About 74 patients are to be enrolled in the trial.

Timeline

Start

2006-12-12

Primary completion

2014-06-26

Completion

2014-09-27

Outcome

Missed primary endpoint

paper The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint PMID 32747013 ↗

Publications

• Background Singer G, Oldt R 3rd, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih IeM. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst. 2003 Mar 19;95(6):484-6. doi: 10.1093/jnci/95.6.484.
• Background Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003 Apr 16;95(8):625-7. doi: 10.1093/jnci/95.8.625.
• Background Pollock PM, Meltzer PS. A genome-based strategy uncovers frequent BRAF mutations in melanoma. Cancer Cell. 2002 Jul;2(1):5-7. doi: 10.1016/s1535-6108(02)00089-2.
• Results Lee JM, Annunziata CM, Hays JL, Cao L, Choyke P, Yu M, An D, Turkbey IB, Minasian LM, Steinberg SM, Chen H, Wright J, Kohn EC. Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment. Gynecol Oncol. 2020 Oct;159(1):88-94. doi: 10.1016/j.ygyno.2020.07.031. Epub 2020 Aug 1.

Drugs

Indications