Temozolomide and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

DISEASE CHARACTERISTICS:

* Histologically confirmed melanoma

  * Unresectable stage IV disease
  * Mucosal and unknown primary disease allowed
* Measurable disease, defined as at least one lesion that can be measured in at least one dimension as ≥ 20 mm (or as ≥ 10 mm if the CT slice thickness is ≤ 5 mm)

  * Measurable lesion must be outside a previously treated area
* Must have 1 paraffin block of primary tumor and/or metastatic tissue available for analysis of MGMT
* No ocular melanoma
* No bleeding skin metastases
* No CNS metastases (even if previously treated) by brain MRI

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* ANC ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Hemoglobin ≥ 90 g/L (transfusion allowed)
* Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT and alkaline phosphatase ≤ 2.5 times ULN (5 times ULN in patients with liver metastases)
* Serum creatinine \< 177 μmol/L
* Proteinuria \< 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection
* INR ≤ 1.5
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 12 months after completion of study treatment
* No other primary tumors within the past 5 years, except adequately controlled limited basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* No history or evidence of CNS disease unrelated to cancer (e.g., uncontrolled seizures) by physical/neurological examination, unless adequately treated with standard medical therapy
* No frequent vomiting or any other pre-existing medical condition that would preclude swallowing and/or absorption of oral medication
* No history or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding
* No uncontrolled hypertension (i.e., systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 100 mm Hg, measured repeatedly, despite adequate treatment with at least two different antihypertensive drugs)
* No clinically significant (i.e., active) cardiovascular disease, including any of the following:

  * Cerebrovascular accident/stroke or myocardial infarction within the past 6 months
  * Unstable angina
  * New York Heart Association (NYHA) class II or greater congestive heart failure
  * Serious cardiac arrhythmia (i.e., ventricular arrhythmia, high-grade atrioventricular-block) that requires medication during the study, interferes with regularity of the study treatment, or is uncontrolled by medication
* No serious non-healing wound, active peptic ulcer, or non-healing bone fracture
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
* No significant traumatic injury within the past 30 days
* No uncontrolled active infection
* No known HIV infection
* No known hypersensitivity to any of the study drugs or excipients
* No evidence of any other disease, metabolic or psychological dysfunction, psychiatric disorder, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect patient compliance with study routines, or places the patient at high risk from treatment-related complications

PRIOR CONCURRENT THERAPY:

* At least 4 weeks since prior adjuvant cytokine therapy (e.g., interleukin, interferon) or vaccine therapy and recovered

  * Prior vaccine therapy for stage IV disease allowed
* Prior perfusion therapy (limb and liver) for loco-regional disease allowed
* No prior chemotherapy for metastatic disease
* No prior bevacizumab or other angiogenic inhibitors
* No prior radiotherapy to lesion(s) selected for measurement
* More than 30 days since prior treatment in a clinical trial
* More than 30 days since prior major surgery with high risk of bleeding
* More than 24 hours since prior minor surgery
* More than 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes

  * Prophylactic use of anticoagulants is allowed (e.g., maintenance of venous catheter)
* More than 10 days since prior and no concurrent acetylsalicylic acid (\> 325 mg/day) or clopidogrel (\> 75 mg/day)
* No other concurrent non-steroidal anti-inflammatory drugs (NSAIDs)
* No concurrent dipyridamole
* No concurrent major surgery
* No concurrent radiotherapy to the target lesions
* No other concurrent experimental drugs or anticancer therapy