SB-715992 in Treating Patients With Metastatic or Recurrent Malignant Melanoma

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

RATIONALE: Drugs used in chemotherapy, such as SB-715992, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well SB-715992 works in treating patients with metastatic or recurrent malignant melanoma.

OBJECTIVES:

• Determine the efficacy of SB-715992, in terms of response rate, in patients with previously untreated metastatic or recurrent malignant melanoma.
• Determine the toxic effects of this drug in these patients.
• Determine the early progression rate and response duration in patients treated with this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Correlate pharmacokinetics with safety and efficacy endpoints of this drug in these patients.
• Correlate β-tubulin and kinesin spindle protein expression in tumor tissue with clinical outcomes in patients treated with this drug.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

All patients are followed at 4 weeks after completion of protocol therapy. Patients with ongoing complete response, partial response, or stable disease are followed every 3 months thereafter until relapse.

PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study within 12-14 months.

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