NCT00387751

Bevacizumab and Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma

A Phase II, Pharmacokinetic (PK), Pharmacodynamic (PD) and Biological Correlative Study of the Efficacy and Safety of Dual Antiangiogenic Inhibition Using Bevacizumab and Sorafenib in Patients With Advanced Malignant Melanoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial is studying how well giving bevacizumab together with sorafenib works in treating patients with unresectable stage III or stage IV malignant melanoma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop the growth of melanoma by blocking blood flow to the tumor. Giving bevacizumab together with sorafenib may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. Determine the clinical biologic activity of sorafenib tosylate and bevacizumab, defined as the sum of complete response, partial response, and prolonged stable disease for ≥ 16 weeks, in patients with unresectable stage III or stage IV malignant melanoma previously treated with at least 2 regimens of immunotherapy, cytokines, biologic therapy, or vaccine therapy or in previously untreated patients who are not appropriate candidates to receive aldesleukin-based treatment. SECONDARY OBJECTIVES: I. Evaluate the safety and tolerability of sorafenib tosylate and bevacizumab in these patients. II. Evaluate the biologic activity of this regimen, in terms of time to progression, progression-free survival at 6 months, and overall survival, in these patients. III. Describe significant pharmacokinetic interactions between bevacizumab and sorafenib tosylate. IV. Characterize the pharmacodynamic relationships between the plasma concentration of sorafenib tosylate and bevacizumab and the effects of treatment on normal organ function and tumor tissue in these patients. V. Identify predictive biomarkers of response to this regimen in these patients. VI. Correlate changes in biological measurements with patient outcomes. OUTLINE: This is an open-label, multicenter study. Patients receive oral sorafenib tosylate on days 1-5, 8-12, 15-19, and 22-26 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression. Blood samples and tumor biopsies are obtained periodically for pharmacokinetic and pharmacodynamic studies. Samples are examined by liquid chromatography, mass spectrometry, immunohistochemistry, gene expression analysis, DNA mutation analysis, and genomic analysis for biological markers. After completion of study treatment, patients are followed for 4 weeks.

Conditions

• Recurrent Melanoma
• Stage III Skin Melanoma
• Stage IV Skin Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Sorafenib Tosylate	Given orally

Timeline

• Start date: 2006-08-01
• Primary completion: 2009-09-01
• Completion: 2010-01-01
• First posted: 2006-10-13
• Last updated: 2017-11-22
• Results posted: 2013-01-17

Locations

1 site across 1 country: United States