Sorafenib, Bevacizumab, and Oxaliplatin in Treating Patients With Metastatic Malignant Melanoma

OBJECTIVES:

- To determine the maximum tolerated dose of sorafenib tosylate when administered with
bevacizumab and oxaliplatin.

- To determine the effect of this treatment regimen on the complete and partial response
rate in patients with metastatic melanoma.

- To determine the effect of this treatment regimen on the progression-free and overall
survival of patients with metastatic melanoma.

OUTLINE: This is a phase I dose-escalation study of sorafenib tosylate followed by a phase
II study.

- Phase I: Patients receive bevacizumab IV over 30-90 minutes and oxaliplatin IV over 2
hours on day 1. Patients also receive oral sorafenib tosylate twice daily on days 1-14.
Treatment repeats every 2 weeks in the absence of disease progression or unacceptable
toxicity.

- Phase II: Patients receive sorafenib tosylate at the maximum tolerated dose and
bevacizumab and oxaliplatin as in phase I.

After completion of study therapy, patients are followed for at least 5 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed melanoma

- Metastatic disease

- Measurable or evaluable non-CNS disease

- Measurable disease, defined as a unidimensionally measurable lesion as
determined by physical exam, x-ray, CT scan, MRI, or other radiographic
procedure

- Evaluable disease, defined as a lesion that can be seen radiographically but is
not unidimensionally measurable

- Previously irradiated lesions with documented progression are allowed
provided there are no other sites of metastatic disease

- No active brain metastases

- Previously treated, responding brain metastases allowed, provided there is
measurable disease outside of the CNS

- At least 3 weeks since prior chemotherapy and 6 weeks since prior
radiotherapy for CNS disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- ANC ≥ 1,200/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min

- Bilirubin ≤ 3.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- EKG with no evidence of serious arrhythmia or recent myocardial infarction

Exclusion criteria:

- Active infection

- Chronic underlying immunodeficiency disease

- Other serious concurrent illness

- Other forms of cancer within 5 years of initial diagnosis except nonmelanoma skin
cancer and cervical cancer

- Congestive heart failure or myocardial infarction within the past 6 months

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

- See Disease Characteristics

- At least 6 weeks since prior radiotherapy

- More than 4 weeks since prior surgery

- Prior biologic therapy allowed

Exclusion criteria:

- Prior cytotoxic agents

- Prior sorafenib tosylate, bevacizumab, or oxaliplatin

- Concurrent biological therapy, except growth factors for anemia, neutropenia, or
thrombocytopenia

- Concurrent radiotherapy, chemotherapy, or surgery