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

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

* 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.

Eligibility 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