A Phase II Study of SB-715992 (NSC 727990) in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant melanoma

- Previously untreated metastatic or recurrent disease

- Considered incurable by standard therapies

- Measurable disease

- At least one unidimensionally measurable lesion ≥ 20 mm by conventional
techniques OR ≥ 10 mm by spiral CT scan

- Bone metastases are not considered measurable disease

- Outside any previously irradiated area

- Patients whose sole site of measurable disease is in a previously
irradiated area are ineligible unless there is evidence of progression or
new lesions documented in the irradiated field

- No known CNS metastases

- CT scans or MRI are not required to rule out CNS metastases unless patient
exhibits neurological signs or symptoms

- Patients with a prior solitary brain metastasis surgically resected with no
evidence of residual disease are eligible provided CT scan or MRI confirms no
evidence of disease within the past 28 days

- Archival paraffin tumor specimen available

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 12 weeks

Hematopoietic

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

Renal

- Creatinine ≤ 1.5 times ULN

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other malignancy except adequately treated nonmelanoma skin cancer, curatively
treated carcinoma in situ of the cervix, or other curatively treated solid tumors
with no evidence of disease for ≥ 5 years

- No other uncontrolled illness

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study participation

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to SB-715992

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 3 months since prior adjuvant immunotherapy

- No prior immunotherapy for metastatic or recurrent disease

Chemotherapy

- No prior chemotherapy, including regional therapy

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy except for low-dose, non-myelosuppressive
radiotherapy

Surgery

- See Disease Characteristics

- At least 4 weeks since prior major surgery

Other

- More than 28 days since prior investigational agents

- More than 14 days since prior and no concurrent use of any of the following CYP3A4
inhibitors or inducers:

- Clarithromycin

- Erythromycin

- Troleandomycin

- Itraconazole

- Ketoconazole

- Fluconazole (≤ 200 mg/day allowed)

- Voriconazole

- Nefazodone

- Fluvoxamine

- Verapamil

- Diltiazem

- Grapefruit juice

- Bitter orange

- Phenytoin

- Carbamazepine

- Phenobarbital

- Oxcarbazepine

- Rifampin

- Rifabutin

- Rifapentine

- Hypericum perforatum (St. John's wort)

- Modafinil

- At least 6 months since prior and no concurrent amiodarone

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer treatment

- No other concurrent investigational therapies