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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: everolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus<br>Daily oral Everolimus 10 mg/day | Drug: everolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | Progression-Free Survival was defined as the duration from the date of registration until the date of disease progression per RECIST or death due to any cause. Patients known to be alive without evidence of disease progression were censored at the date of last contact. Disease progression was defined as a >= 20% increase over nadir in the sum of longest diameters of target lesions, unequivocal progression of non-target lesions in the opinion of the treating investigator, appearance of new lesions, symptomatic deterioration, or death due to disease | Every 8 weeks until disease progression, up to 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | A response was defined as either a confirmed or unconfirmed complete or partial responses as defined by RECIST. A complete response (CR) was defined as the disappearance of all disease. A partial response (PR) was defined as a >= 30% decrease in the sum of longest diameters of target lesions. A CR or PR was considered confirmed if two consecutive determinations were made at least 4 weeks apart. | Every 8 weeks until disease progression, up to 3 years. | 
| Overall Survival | Overall survival was defined as the duration between the date of enrollment and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. | Every 8 weeks until disease progression, up to 3 years. | 
| Frequency and Severity of Toxicities |  | Weekly during the first 8 weeks of treatment, then every 4 weeks while on treatment, then every 8 weeks until disease progression, then every 6 months thereafter. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent malignant mesothelioma, stage II malignant mesothelioma, stage III malignant mesothelioma, stage IV malignant mesothelioma