• 8-week progression free survival [ Designated as safety issue: No ]
  

• Confirmed tumor response (complete response or partial response) [ Designated as safety issue: No ]
  
• Clinical response rate [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the anti-tumor activity of carboplatin, paclitaxel, and bevacizumab, in terms of progression-free survival, in patients with unresectable stage IV melanoma.
• Determine the toxicity profile of this regimen in these patients.

Secondary

• Determine the distribution of overall survival times in patients treated with this regimen.
• Determine the response rate in patients treated with this regimen.
• Determine the changes in blood levels of vascular endothelial growth factor in patients treated with this regimen.
• Determine the changes in immune homeostasis in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV over 30 minutes on day 1, paclitaxel IV over 1 hour on days 1, 8, and 15, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• More than 4 months

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed)
• No active bleeding

Hepatic

• 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

Renal

• Creatinine ≤ 1.5 times ULN
• Urine protein creatinine ratio ≤ 0.5 OR
• Urine protein < 1 g/24-hr urine collection

Cardiovascular

• 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 mm Hg despite antihypertensive therapy)
• No clinically significant stroke within the past 6 months
• No deep vein thrombosis within the past year
• No other vascular abnormality

Pulmonary

• No pulmonary embolus within the past year

Gastrointestinal

• No history of abdominal fistula
• No gastrointestinal perforation
• No intra-abdominal abscess within the past 4 weeks

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• 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

Chemotherapy

• No more than 1 prior systemic chemotherapy regimen
• No prior carboplatin or paclitaxel
• No other concurrent chemotherapy

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to > 25% of bone marrow
• No concurrent radiotherapy

Surgery

• 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

Other

• 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