A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma

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