S0722: Everolimus in Treating Patients With Pleural Malignant Mesothelioma That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• To determine the 4-month progression-free survival in patients with unresectable malignant pleural mesothelioma treated with everolimus.

Secondary

• To determine the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in patients with measurable disease by RECIST and modified RECIST criteria.
• To determine overall survival of these patients.
• To evaluate the frequency and severity of toxicities associated with this treatment regimen.

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

• 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