A Phase II Study Evaluating the Efficacy of VEGF Trap in Patients With Recurrent Inoperable Stage III or Stage IV Melanoma

Inclusion Criteria:

- Histologically confirmed stage III or IV melanoma

- Cutaneous, ocular, or mucosal melanoma allowed

- Recurrent, inoperable disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- No evidence of CNS disease, including primary brain tumor or brain metastases

- No brain metastases by MRI or CT scan within the past 4 weeks

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 3 months

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine
collection

- PT INR ≤ 1.5 unless on full-dose warfarin

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to agents used in the study

- No serious or nonhealing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No significant traumatic injury within the past 28 days

- No clinically significant cardiovascular disease, including any of the following:

- Cerebrovascular accident within the past 6 months

- Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or
systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg within the past 3 months

- Myocardial infarction, coronary artery bypass graft, or unstable angina within
the past 6 months

- New York Heart Association class III-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Unstable angina pectoris within the past 6 months

- Clinically significant peripheral vascular disease within the past 6 months

- Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within
the past 6 months

- No evidence of bleeding diathesis or coagulopathy

- No concurrent uncontrolled illness, including, but not limited to any of the
following:

- Ongoing or active infection

- Psychiatric illness or social situation that would preclude study compliance

- Recovered from all prior therapy and major surgery

- No prior chemotherapy or hormonal therapy

- More than 7 days since prior core visceral organ biopsy

- More than 4 weeks since prior biologic therapy or radiotherapy

- More than 28 days since prior major surgery or open biopsy

- No concurrent major surgery

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- Concurrent full-dose warfarin with PT INR > 1.5 allowed provided the following
criteria are met:

- INR in range (2-3) on a stable dose of oral anticoagulant or low molecular
weight heparin

- No active bleeding or pathological condition that carries a high risk of
bleeding (e.g., tumor involving major vessels or known varices)