Phase II Trial of mTOR Inhibitor, Everolimus (RAD001), in Malignant Pleural Mesothelioma (MPM)
Phase II Trial of mTOR Inhibitor, Everolimus (RAD001), in Malignant Pleural Mesothelioma (MPM)
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well everolimus works in treating patients with pleural malignant mesothelioma that cannot be removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 3 years.
DISEASE CHARACTERISTICS:
Histologically confirmed malignant pleural mesothelioma
Must have measurable or nonmeasurable disease by RECIST or modified RECIST criteria
Must have received prior systemically administered* platinum-based chemotherapy and meets the following criteria:
No known CNS metastases
PATIENT CHARACTERISTICS:
Zubrod performance status 0-1
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Serum bilirubin normal
AST or ALT ≤ 1.5 times upper limit of normal (ULN)
Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
Not pregnant or nursing
Fertile patients must use effective contraception
No evidence of bleeding diathesis or coagulopathy
Previous pulmonary embolism allowed provided the patient is on therapeutic low molecular weight heparin injections or warfarin AND no evidence of bleeding
No pathologic condition other than mesothelioma that carries a high risk of bleeding
No known HIV positivity
No gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for IV alimentation, or active peptic ulcer disease
No other prior malignancy allowed except for any of the following:
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from all prior therapy
At least 28 days since prior systemic therapy (42 days for nitrosoureas or mitomycin C)
At least 28 days since prior thoracic or other major surgery (e.g., pleurectomy or pleurodesis) and no anticipated need for major surgical procedures during study
At least 14 days since prior radiotherapy
No prior surgical procedure affecting absorption
No prior chronic, systemic corticosteroids or other immunosuppressive agent, except corticosteroids equivalent to prednisone ≤ 20 mg daily
No prior mTOR inhibitor therapy (i.e., rapamycin, everolimus, or temsirolimus)
No concurrent immunization with attenuated live vaccines
No concurrent antiretroviral therapy for HIV-positive patients
No other concurrent investigational therapy
No other concurrent anticancer agents
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