| Inclusion Criteria: | 1) Patients must have histologically confirmed diagnosis of unresectable malignant pleural mesothelioma.
2) Patients must have measurable or non-measurable disease documented by CT scan. Measurable disease must be assessed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration. The CT from a combined PET/CT must not be used to document measurable disease unless it is of diagnostic quality. All disease must be assessed and documented.
3) Patients must have had prior systemically administered platinum-based chemotherapy. Pleural space washing with cisplatin does not constitute systemic administration. No more than two prior systemic therapeutic regimens are allowed (including biologics, targeted and immunotherapies), and at least one regimen must have been platinum-based. Neoadjuvant and/or adjuvant systemic therapy will not be counted as a prior regimen, assuming at least 12 weeks have elapsed between the end of neoadjuvant/adjuvant therapy and development of progressive disease.
4) Continuation of #3. Patients must have completed systemic therapy (including any chemotherapy, biologics, targeted and immunotherapies) >/= 28 days (42 days for nitrosoureas or mitomycin C) prior to registration and have recovered from adverse events due to agents administered
5) Patients may have received prior surgery (e.g., pleurectomy, pleurodesis) provided that at least 28 days have elapsed since surgery (thoracic or other major surgeries) and patients have recovered from all associated toxicities at the time of registration. There must be no anticipated need for major surgical procedures during protocol treatment.
6) Patients must not have known CNS metastases.
7) Institutions must offer patients participation in correlative studies.
8) Patients may have received prior radiation therapy provided that at least 14 days have elapsed since the last treatment and patients have recovered from all associated toxicities at the time of registration.
9) Patients must not have received chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone </= 20 mg. Patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first planned treatment with everolimus. Topical or inhaled corticosteroids are allowed.
10) Patients must not have had prior mTOR inhibitor therapy (rapamycin, everolimus, temsirolimus [CCI-779], AP23573).
11) Patients must not be planning to receive immunization with attenuated live vaccines.
12) Patients must have a Zubrod Performance Status of 0 - 1.
13) All patients must be 18 years of age or older.
14) Patients must have adequate hematologic function as documented by an ANC >/= 1,500/mcl and a platelet count >/= 100,000/mcl obtained within 28 days prior to registration.
15) Patients must have adequate hepatic function as evidenced by serum bilirubin </= institutional upper limit of normal (IULN). SGOT (AST) or SGPT (ALT) must be </= 1.5 x IULN. These tests must be obtained within 28 days prior to registration.
16) Patients must have a serum creatinine </= 1.5 x IULN or a calculated or measured creatinine clearance >/= 50 mL/min using the following formula. These tests (including creatinine [mg/dl] if using calculated creatinine clearance) must be obtained within 28 days prior to registration. Calculated Creatinine Clearance = (140-age) x wt (kg) x 0.85 (if female) 72 x creatinine (mg/dl)
17) Patients must have no evidence of bleeding diathesis or coagulopathy. However, patients may have had a previous pulmonary embolism provided they are on therapeutic low molecular weight heparin (LMWH) injections or warfarin, and have no evidence of bleeding. If patient is on therapeutic wrfarin, they must have an international normalized ratio (INR) < 1.5 within 28 days prior to registration. Patients must have no pathologic condition other than mesothelioma that carries a high risk of bleeding.
18) Patients must not be known to be HIV-positive and on antiretroviral therapy because of the potential for pharmacokinetic interactions with everolimus.
19) Patients must not have gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
20) Patients must not be pregnant or nursing because of increased risk of harm to a nursing infant or fetus including fetal death from the chemotherapeutic agents. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
21) No other prior malignancy is allowed except for 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, or any other cancer from which the patient has been disease-free for 5 years.
22) All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
23) At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base. |