Bevacizumab and Sorafenib in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma
Condition: Recurrent Melanoma; Stage III Skin Melanoma; Stage IV Skin Melanoma
MeSH terms: Melanoma; Skin Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Bevacizumab; Laboratory Biomarker Analysis; Pharmacological Study; Sorafenib Tosylate
Intervention type(s): Biological; Other; Other; Drug
Intervention description(s): Given IV; Correlative studies; Correlative studies; Given orally
Other intervention name(s): Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Avastin; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; BAY 43-9006 Tosylate; BAY 54-9085; Nexavar; sorafenib
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Sorafenib; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment