OBJECTIVES:

Primary

• Determine the objective response rate in patients with brain metastases secondary to melanoma treated with temozolomide and thalidomide.

Secondary

• Determine the toxic effects of and tolerance to this regimen in these patients.
• Determine the objective response rate in extracranial metastases of patients treated with this regimen.
• Determine the time to first disease progression (intra- or extracranial) in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral temozolomide once daily on days 1-42 and oral thalidomide once daily on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses of therapy beyond CR.

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

PROJECTED ACCRUAL: A total of 21-50 patients will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic melanoma

• Clinical evidence of brain metastases

  • At least 1 unidimensionally measurable brain lesion at least 2.0 cm by conventional techniques OR at least 1.0 cm by spiral CT scan or MRI

    • The following lesions are not considered measurable:

      • 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 situated in a previously irradiated area, unless new growth is documented

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• CTC 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• AST and ALT no greater than 2.5 times upper limit of normal (ULN)
• Lactic dehydrogenase no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No history of active angina
• No history of significant ventricular arrhythmia
• No history of deep vein thrombosis
• No myocardial infarction within the past 6 months
• No acute abnormality by EKG
• No uncontrolled arrhythmia

Pulmonary

• No history of pulmonary embolism

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 1 highly-effective and 1 additional method of contraception for 28 days before, during, and for 4 weeks after study participation
• No known HIV disease
• Thyroid-stimulating hormone normal
• Serum anticonvulsant levels normal (for patients on anticonvulsants)
• No frequent vomiting and/or any other medical condition (e.g., partial bowel obstruction) that would preclude oral medication intake
• No preexisting neuropathy greater than grade 1
• No uncontrolled seizures
• No other concurrent medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior cytokines

  • Biologic agents used as adjuvants, vaccines, and cellular therapies do not require a 4-week washout period
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• No more than 1 prior chemotherapy regimen
• No prior chemotherapy for brain metastases
• No prior continuous daily temozolomide
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except steroids and hormones administered for non-disease-related conditions (e.g., insulin for diabetes) or for control of intracranial edema from brain metastases

Radiotherapy

• See Disease Characteristics
• Prior whole brain radiotherapy (WBRT) allowed provided patient has progressive disease in a measurable CNS lesion
• Prior stereotactic radiotherapy allowed provided patient has progressive disease in a measurable CNS lesion
• At least 4 weeks since prior WBRT
• At least 3 weeks since prior stereotactic radiosurgery
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior surgical resection

Other

• No concurrent warfarin or heparin products or their derivatives
• No concurrent antiplatelet therapy (e.g., daily aspirin, ibuprofen, or clopidogrel bisulfate)
• No concurrent bisphosphonates (e.g., zoledronate)