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

This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage IV melanoma, recurrent melanoma Read More

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