RANDOMIZED PHASE II STUDY COMPARING TWO SCHEDULES OF TEMOZOLOMIDE IN COMBINATION WITH BAY43-9006 IN PATIENTS WITH ADVANCED MELANOMA

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed melanoma

- Metastatic or unresectable disease

- Measurable disease by RECIST criteria

- Cutaneous lesions measuring at least 1 cm will be considered measurable disease

- Brain metastases allowed provided patient completed radiotherapy, if radiotherapy was
clinically indicated at the time of diagnosis, AND discontinued steroids prior to
study enrollment

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- WBC ≥ 3,000/mm³

- Absolute granulocyte count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Serum creatinine ≤ 2.0 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN (< 3.0 times ULN if Gilbert's disease is present)

- AST or ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if liver metastases are present)

- INR ≤ 1.5 (if on anticoagulation, baseline INR must be < 1.5 before starting
anticoagulation)

- PTT normal

- No other concurrent malignancies, except basal cell or squamous cell skin cancer,
carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast

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

- Ongoing or active infection requiring parenteral antibiotics

- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction, unstable angina)

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

- Serious cardiac arrhythmia requiring medication

- Peripheral vascular disease ≥ grade II within the past year

- Psychiatric illness/social situation that would limit compliance with study
requirements

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No HIV positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from all prior therapy

- Prior radiotherapy allowed

- If radiotherapy has been administered to a lesion, there must be radiographic
evidence of progression of that lesion for that lesion to constitute measurable
disease or to be included in the measured target lesions

- Prior temozolomide or sorafenib tosylate allowed

- At least 4 weeks since prior chemotherapy

- At least 4 weeks since prior active immunotherapy (aldesleukin, interferon,
sargramostim [GM-CSF], or CTLA-4)

- At least 4 weeks since prior and no other concurrent investigational anticancer
therapy (except vaccines)

- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin,
carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)