Phase II Trial of mTOR Inhibitor, Everolimus (RAD001), in Malignant Pleural Mesothelioma (MPM)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant pleural mesothelioma

- Unresectable disease

- 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 more than 2 prior systemic therapeutic regimens allowed (including biologics,
targeted, and immunotherapies)

- At least 1 regimen must have been platinum-based

- Neoadjuvant and/or adjuvant systemic therapy is not counted as a prior regimen,
assuming ≥ 12 weeks have elapsed between the end of neoadjuvant/adjuvant therapy
and development of progressive disease NOTE: *Pleural space washing with
cisplatin does not constitute systemic administration

- 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

- Patients on therapeutic warfarin must have an INR of < 5 within 28 days
prior to registration

- 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:

- Adequately treated basal cell or squamous cell skin cancer

- In situ cervical cancer

- Adequately treated stage I or II cancer from which the patient is currently in
complete remission

- Any other cancer from which patient has been disease-free for 5 years

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

- Must have been on a stable dosage regimen for ≥ 4 weeks

- Topical and inhaled corticosteroids allowed

- 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