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

Inclusion Criteria

• •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