A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma
A Phase II Study of Temozolomide and Everolimus (RAD001) Therapy for Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Giving everolimus together with temozolomide may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving everolimus together with temozolomide works in treating patients with stage IV melanoma that cannot be removed by surgery
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once a day on days 1-5, 8-12, 15-19, 22-26, and 29-33 and oral temozolomide once a day on days 8-12 for course 1 only. For course 2 and all subsequent courses, patients receive oral everolimus once a day on days 1-5, 8-12, 15-19, and 22-26 and oral temozolomide once a day on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
All patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for relative numbers of T, B, and NK cells via flow cytometry, quantitative immunoglobulin levels (IgG, IgM, and IgA), Tetramer/ELISPOT CTL frequencies to CMV/EBV immunodominant antigens, V beta T cell spectratyping, and VEGF levels via ELISA.
After completion of study treatment, patients are followed every 8 weeks.
DISEASE CHARACTERISTICS:
Histologically confirmed melanoma with manifestations of metastatic disease.
Unresectable stage IV malignant melanoma with measurable disease
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:
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:
Grand Junction, Colorado 81502, United States
Ottawa, Illinois 61350, United States
Peoria, Illinois 61615, United States
Beech Grove, Indiana 46107, United States
La Porte, Indiana 46350, United States
Des Moines, Iowa 50309, United States
Des Moines, Iowa 50314, United States
Wichita, Kansas 67214, United States
Minneapolis, Minnesota 55407, United States
Robbinsdale, Minnesota 55422-2900, United States
Billings, Montana 59101, United States
Missoula, Montana 59807, United States
Allentown, Pennsylvania 18105, United States
Spartanburg, South Carolina 29303, United States
Sioux Falls, South Dakota 57117-5039, United States
Green Bay, Wisconsin 54301-3526, United States