Temozolomide, Thalidomide, and Lomustine in Treating Patients With Unresectable Stage III or Stage IV Melanoma

OBJECTIVES:

Primary

• Determine the antitumor activity of temozolomide, thalidomide, and lomustine, in terms of objective response rate, in patients with unresectable stage III or stage IV melanoma.

Secondary

• Determine the toxicity profile of this regimen in these patients.
• Determine the duration of response and overall survival of patients treated with this regimen.

OUTLINE: Patients receive oral temozolomide on days 1-42, oral thalidomide on days 1-56, and oral lomustine on days 1 and 29. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic malignant melanoma

• Unresectable stage III OR stage IV disease
• Ocular, mucosal, and cutaneous melanoma allowed
• Measurable disease

• Indicator lesions within a prior radiotherapy field must have recent evidence of disease progression
• Indicator lesions must be distinct from the surgical and/or radiation changes induced by prior local therapies
• No more than 2 symptomatic hemorrhagic lesions in the brain

• No hemorrhagic lesion(s) greater than 1 cm in diameter

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN
• Lactic dehydrogenase no greater than 2 times ULN

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No history of severe cardiovascular disease
• No myocardial infarction within the past 6 months
• No unstable angina
• No New York Heart Association class III or IV congestive heart failure
• No ventricular arrhythmia
• No uncontrolled arrhythmia

Gastrointestinal

• No frequent vomiting
• No other medical condition that would preclude oral medication intake (e.g., partial bowel obstruction)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 4 weeks after study participation
• HIV negative
• No AIDS-related illness
• No serious infection requiring IV antibiotics
• No other uncontrolled medical illness that would preclude study participation
• No other malignancy within the past 2 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or T1a or b prostate cancer meeting all of the following criteria:

• Detected incidentally at transurethral resection of the prostate (TURP)
• Comprises less than 5% of resected tissue
• Prostate-specific antigen normal since TURP

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 weeks since prior immunotherapy or biologic therapy
• No concurrent immunotherapy

Chemotherapy

• No prior systemic chemotherapy for melanoma
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior focused radiotherapy for brain metastases
• At least 3 weeks since prior radiosurgery
• At least 4 weeks since prior whole brain radiotherapy
• At least 3 weeks since prior interstitial brachytherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 3 weeks since prior surgery for brain metastases
• At least 3 weeks since prior surgery requiring general anesthesia

Other

• Recovered from all prior therapies