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

Phase 2

Completed

Conditions: Recurrent Melanoma
Stage III Skin Melanoma
Stage IV Skin Melanoma

Interventions: Biological: Bevacizumab
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Sorafenib Tosylate

Registration Number: NCT00387751

Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	Pharmacological 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.
Arm I	Laboratory Biomarker Analysis	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.
Arm I	Bevacizumab	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.
Arm I	Sorafenib Tosylate	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.

Primary Outcome Measures

Name	Time	Method
Response	4 months	Clinical biologic activity of treatment, defined as the sum of complete response, partial response, and prolonged stable disease for ≥ 16 weeks, upon treatment with the combination of sorafenib and bevacizumab, in patients with advanced metastatic melanoma previously treated with immunotherapy or in previously untreated patients who are not appropriate candidates to receive IL-2-based treatment. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started of the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Secondary Outcome Measures

Name	Time	Method
Survival	6 months	Determined by time to progression, progression-free suvival, and overall survival.
Safety and Tolerability	6 months	Safety and tolerability of treatment, in terms of toxicity profile and incidence and rating of toxicity, according to NCI CTCAE v3.0 criteria.