Everolimus in Treating Patients With Stage IV Melanoma

OBJECTIVES:

Primary

• Determine the median time to disease progression in patients with stage IV malignant melanoma treated with everolimus.

Secondary

• Determine the median overall survival of patients treated with this drug.
• Determine the clinical benefit rates (i.e., stable disease, partial remission, and complete response rates) in patients treated with this drug.
• Determine the toxicity profile of this drug in these patients.
• Determine changes in serum vascular endothelial growth factor levels in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months until disease progression and then every 4 months for up to 5 years after registration.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma for which no known standard or potentially curative therapy exists or has been proven to extend life expectancy

• Stage IV disease
• Measurable disease

• At least 1 lesion ≥ 20 mm by CT scan or MRI OR ≥ 10 mm by spiral CT scan
• No intracranial disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• No bleeding diathesis

Hepatic

• AST ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 ULN
• INR ≤ 1.5

Renal

• Creatinine ≤ 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to refrain from foods high in fat content
• No uncontrolled infection
• No immunosuppression from any cause (e.g., known HIV infection)
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer treated with local resection only
• No other severe condition that would preclude study participation or compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy or biologic therapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior sirolimus or its analogues for any indication
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent steroids

Radiotherapy

• More than 4 weeks since prior radiotherapy to head and neck area
• More than 4 weeks since prior radiosurgery
• No prior radiotherapy to > 30% of bone marrow
• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 1 week since prior and no concurrent CYP3A4 inducers
• No concurrent warfarin
• No concurrent cytotoxic agents
• No other concurrent experimental drugs
• No other concurrent immunosuppressive therapy