s0722: everolimus in treating patients with pleural malignant mesothelioma that cannot be removed by surgery

Conditions: Malignant Mesothelioma

Summary: 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

Keywords: recurrent malignant mesothelioma stage ii malignant mesothelioma stage iii malignant mesothelioma stage iv malignant mesothelioma