Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed melanoma with manifestations of metastatic disease.
• •Unresectable stage IV malignant melanoma with measurable disease
• •* Measurable disease defined as at least one lesion with the longest diameter measured as ≥ 20 mm by CT scan or MRI scan OR ≥ 10 mm by spiral CT
• •No previously untreated or unstable active brain metastases within the past 3 months
• •No known standard therapy for this disease that is potentially curative or proven capable of extending life expectancy
• •PATIENT CHARACTERISTICS:
• •ECOG performance status 0-2
• •Life expectancy ≥ 12 weeks
• •ANC ≥ 1,500/μL
• •Platelet count ≥ 100,000/μL
• •Hemoglobin ≥ 9.0 g/dL
• •Alkaline phosphatase ≤ 3 times institutional upper limit of normal (ULN)
• •Creatinine ≤ 1.5 times ULN
• •AST ≤ 3 times ULN
• •INR ≤ 1.5
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients and their partners must use effective contraception during and for ≥ 8 weeks after completion of study treatment
• •Able to return to a NCCTG institution for follow-up
• •Able to forego foods high in fat content 2 hours prior to and 2 hours after administration of everolimus therapy
• •Able to provide blood samples for research purposes
• •No hypersensitivity to temozolomide, dacarbazine, or any analog of sirolimus
• •No history of malignancy within the past 5 years except for basal cell or squamous cell carcinoma of the skin treated with local resection only
• •No immunosuppression from any cause, including known HIV infection or chronic immunosuppressive therapy
• •No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
• •No serious medical condition that may make it unsafe for a patient to enroll in study, including any of the following:
• •* Severely impaired lung function (FEV1 \< 1 liter), unstable angina pectoris (ongoing symptoms), ongoing symptomatic congestive heart failure (i.e., NYHA class I-IV) refractory to appropriate therapy, or myocardial infarction within the past 6 months, or serious uncontrolled cardiac arrhythmia
• •* Uncontrolled diabetes in spite of optimal therapy (i.e., a history of fasting serum glucose \> 150 mg/dL)
• •* Any active (acute or chronic) or uncontrolled infection/disorders
• •* Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the study treatment
• •* Liver disease (i.e., uncompensated cirrhosis or active hepatitis with elevated liver enzymes)
• •No bleeding diathesis
• •No concurrent severe condition that would make it undesirable for the patient to participate in this trial or that would jeopardize compliance with the trial
• •PRIOR CONCURRENT THERAPY:
• •Must have recovered from effects of prior antineoplastic therapy
• •At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
• •At least 4 weeks since prior immunotherapy
• •At least 4 weeks since prior biologic therapy
• •At least 4 weeks since prior radiosurgery
• •At least 4 weeks since prior investigational therapy for melanoma
• •No prior small bowel resection that may significantly alter the absorption of everolimus
• •No prior sirolimus or its analogues
• •No prior radiotherapy to \> 30% of bone marrow
• •No concurrent drugs that may induce CYP3A4 activity
• •No concurrent warfarin
• •No concurrent grapefruit or grapefruit juice
• •No concurrent use or planned use of vaccines containing live virus