Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer
- 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.
- To determine the safety and effectiveness 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 at different treatment intervals.
- 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.
- 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 (MRI and PET) are done before treatment, 3 days after beginning treatment, and 6 weeks into therapy.
- 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.
Genetic: proteomic profiling
Other: laboratory biomarker analysis
Procedure: dynamic contract-enhanced magnetic resonance imaging
Procedure: needle biopsy
Procedure: positron emission tomography
Radiation: fludeoxyglucose F 18
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Sorafenib and Bevacizumab in Epithelial Ovarian, Fallopian, and Peritoneal Cancer|
- Clinical response rate. [ Designated as safety issue: No ]
- Progression-free survival after 6 or more courses of treatment. [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Biological markers [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Estimated Study Completion Date:||October 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Sorafenib is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro, but it also inhibits p38, c-kit, VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf.
Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human 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.
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.
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 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.
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. DCE-MRI and 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 RECIST criteria.
Approximately 74 patients will be needed to achieve the objectives of the trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00436215
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Christina M Annunziata, M.D.||National Cancer Institute (NCI)|