• Clinical response [ Designated as safety issue: No ]
  
• Safety [ Designated as safety issue: Yes ]
  
• Time to treatment failure [ Designated as safety issue: No ]
  
• Biochemical effects [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine clinical response in patients with metastatic malignant melanoma treated with tipifarnib.
• Determine the safety of this drug in these patients.
• Determine the time to treatment failure in patients treated with this drug.
• Determine the biochemical effects of this drug on tumor tissue in these patients.

OUTLINE: Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for at least 2 courses and for a maximum of 2 years in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses beyond CR.

Patients who discontinue therapy due to toxicity or complete response are followed every 3 months for 2 years after study entry. Patients who discontinue therapy due to disease progression are followed every 6 months for 2 years after study entry. Patients with stable or partially responding disease who complete treatment are followed at 2 years after study entry.

PROJECTED ACCRUAL: A total of 14-40 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed cutaneous melanoma

  • Clinical evidence of distant, metastatic, nonresectable regional lymphatic, or extensive in-transit recurrent disease
• At least 2 cutaneous lesions amenable to excisional biopsy

• Measurable disease

  • Disease remaining after the first excisional biopsy must be measurable

  • The following are considered non-measurable disease:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Lesions in a previously irradiated area
• No history of brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL

Renal

• Creatinine no greater than 2.0 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No allergy to azole drugs (e.g., ketoconazole)
• No allergy to compounds of similar structure to tipifarnib

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No more than 1 prior immunotherapy regimen for advanced melanoma

  • One additional adjuvant immunologic regimen (e.g., interferon alfa) allowed
• More than 4 weeks since prior immunotherapy

Chemotherapy

• No prior chemotherapy for any stage of melanoma

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• No antacids (magnesium- or aluminum-containing formulations) within 2 hours of tipifarnib administration