Carboplatin, Paclitaxel, and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

Inclusion Criteria:

• Histologically confirmed melanoma

  • Unresectable stage IV disease
  • Evidence of metastatic disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No radiologically confirmed invasion of adjacent organs (e.g., duodenum or stomach)
• No tumor invasion of major blood vessels
• No history of primary brain tumor or other CNS disease
• No brain metastases by MRI or CT scan
• Performance status - ECOG 0-2
• More than 4 months
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed)
• No active bleeding
• Bilirubin ≤ 1.5 mg/dL
• AST ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• INR ≤ 1.5 times ULN
• PTT normal
• No known esophageal varices
• Creatinine ≤ 1.5 times ULN
• Urine protein creatinine ratio ≤ 0.5
• Urine protein < 1 g/24-hr urine collection
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No myocardial infarction within the past 6 months
• No unstable angina within the past 6 months
• No clinically significant peripheral vascular disease
• No uncontrolled hypertension (i.e., blood pressure ≥ 150/90 mmHg despite antihypertensive therapy)
• No clinically significant stroke within the past 6 months
• No deep vein thrombosis within the past year
• No other vascular abnormality
• No pulmonary embolus within the past year
• No history of abdominal fistula
• No gastrointestinal perforation
• No intra-abdominal abscess within the past 4 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy
• No other pathological condition that would confer a high risk of bleeding
• No active infection requiring parenteral antibiotics
• No serious nonhealing wound (including wounds healing by secondary intention), ulcer, or bone fracture
• No peripheral neuropathy ≥ grade 2
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to the study drugs
• No uncontrolled seizures
• No other uncontrolled illness
• No significant traumatic injury within the past 4 weeks

• No prior antivascular endothelial growth factors (VEGF), including any of the following:

  • Bevacizumab
  • VEGF Trap
  • Anti-VEGF receptor monoclonal antibody
  • Small molecular tyrosine kinase inhibitors of VEGF receptors
• No more than 1 prior systemic chemotherapy regimen
• No prior carboplatin or paclitaxel
• No other concurrent chemotherapy
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to > 25% of bone marrow
• No concurrent radiotherapy
• At least 4 weeks since prior major surgical procedure or open biopsy
• At least 1 week since prior fine-needle aspiration or core biopsy
• No concurrent major surgery
• More than 4 weeks since prior systemic therapy

• No concurrent full-dose oral or parenteral anticoagulation

  • No concurrent antiplatelet therapy except low-dose aspirin (i.e., 81 mg of oral aspirin daily) allowed
• No other concurrent experimental drugs