A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologic confirmed diagnosis of malignant melanoma

- Stage IV disease

- Not amenable to surgery

- Measurable disease with at least one lesion whose longest diameter can be measured as
≥ 20 mm by CT or MRI scans OR ≥ 10 mm by spiral CT

- No disease that is measurable by physical examination only

- No brain metastases per MRI or CT

- No radiographically documented invasion of adjacent organs (duodenum, stomach, etc.)
or tumor invading major blood vessels

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-1

- Life expectancy ≥ 4 months

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL (transfusion allowed)

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 mg/dL (unless Gilbert syndrome)

- AST ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Urine protein:creatinine ratio < 1.0 at screening OR proteinuria < 2+ by urine
dipstick or protein ≤ 1 g by 24-hour urine collection

- Negative serum pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective contraception

Exclusion criteria:

- Active infection requiring parenteral antibiotics

- Poorly controlled high blood pressure (≥ 150 mm Hg systolic and/or 100 mm Hg
diastolic) despite treatment

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Myocardial infarction or unstable angina within the past 6 months

- Clinically significant peripheral vascular disease

- Deep venous thrombosis or pulmonary embolus within the past year

- Active bleeding or pathological conditions that carry high risk of bleeding (e.g.,
known esophageal varices)

- Serious, non-healing wound (including wounds healing by secondary intention), ulcer
or bone fracture

- Abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within the
past 6 months

- History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.)

- Clinically significant stroke or TIA within the past 6 months

- Seizures not controlled with standard medical therapy

- Peripheral neuropathy ≥ grade 2

- History of other malignancy within the past 5 years except basal cell or squamous
cell carcinoma of the skin treatable with local resection only or carcinoma in situ
of the cervix

- Significant traumatic injury within the past 4 weeks

- History of hypertensive crisis or hypertensive encephalopathy

- Active or recent (≤ 30 days) history of hemoptysis (≥ ½ teaspoon of bright red blood
per episode)

- Known hypersensitivity to any of the components of bevacizumab

- Known to be HIV positive

- Current or known history of hepatitis

PRIOR CONCURRENT THERAPY:

- Prior adjuvant chemotherapy and/or immunotherapy for this cancer allowed

- No prior treatment with agents disrupting VEGF activity (i.e., bevacizumab,
VEGF-trap, anti-VEGFR Mab)

- No ongoing need for full-dose oral or parenteral anticoagulation

- No ongoing anti-platelet treatment other than low-dose aspirin (i.e., aspirin 81 mg
daily)

- No other investigational agents within the past 4 weeks

- No major surgical procedure or open biopsy within the past 4 weeks

- No fine needle aspirations or core biopsies within the past 7 days

- No prior chemotherapy in the metastatic setting

- No prior treatment with sunitinib malate or sorafenib

- No prior treatment with any taxane-based chemotherapy

- Patients who have had > 25% of their functional bone marrow irradiated are not
eligible for this trial

- No adjuvant radiation therapy within the past 4 weeks

- More than 2 weeks since prior and no concurrent palliative radiation therapy

- No concurrent major surgical procedure

- No concurrent participation in another clinical study for procedures or agents that
treat the same primary study malignancy