Efficacy of Bevacizumab Monotherapy in Treatment of Metastatic Melanoma

LEVEL A (second line): after confirmed progression on standard first line treatment with dacarbazine.

LEVEL B (first line): when objective clinical response is observed in LEVEL A, patients will be included for first line treatment with bevacizumab

Inclusion Criteria:

• Histologically confirmed metastatic (unresectable) melanoma and with progressive disease
• WHO performance status 0-2
• Age >18 years
• Able to undergo outpatient treatment
• Patients must have clinically and/or radiographically documented measurable disease according to RECIST criteria
• At least 4 weeks since adjuvant interferon alpha
• Recovered from prior chemotherapy
• Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start. Biopsy or fine needle aspiration within 5 days prior to study treatment start. Central venous line placement must be inserted at least 5 days prior to treatment start.
• Minimum required laboratory data:

Hematology: absolute granulocytes > 1.0 x 109/L platelets > 100 x 109/L Biochemistry: bilirubin < 1.5 x upper normal limit serum creatinine within normal limits INR < 1.5

• Before patient registration/randomization, written informed consent must be given according to national and local regulations.

Exclusion Criteria:

• No pregnant or lactating patients can be included
• No prior interferon alpha or IL-2 for metastatic disease
• No more than 1 prior chemotherapy regimen for metastatic disease
• No clinical evidence of coagulopathy
• No brain metastases
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No history of thrombosis
• No full-dose oral coumarin-derived anticoagulants (INR>1.5) or heparin, thrombolytic agents, or chronic, daily treatment with aspirin (>325 mg/day)
• No non-steroidal anti-inflammatory medications (those known to inhibit platelet function at doses used to treat chronic inflammatory diseases)
• No uncontrolled hypertension
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial