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

Primary Outcome Measures:

• 4-month progression-free survival [ Designated as safety issue: N]

Secondary Outcome Measures:

• 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 [ Designated as safety issue: N]
• Overall survival [ Designated as safety issue: N]
• Frequency and severity of toxicities [ Designated as safety issue: Yes ]

Objectives:

• Primary
  • Tdetermine the 4-month progression-free survival in patients with unresectable malignant pleural mesothelioma treated with everolimus.
• Secondary
  • Tdetermine 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.
  • Tdetermine overall survival of these patients.
  • Tevaluate 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 administeredplatinum-based chemotherapy and meets the following criteria:
  • Nmore 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
• Nknown 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
• Nevidence of bleeding diathesis or coagulopathy
  • Previous pulmonary embolism allowed provided the patient is on therapeutic low molecular weight heparin injections or warfarin AND nevidence of bleeding
    • Patients on therapueutic warfarin must have an INR of < 5 within 28 days prior tregistration
• Npathologic condition other than mesothelioma that carries a high risk of bleeding
• Nknown HIV positivity
• Ngastrointestinal tract disease resulting in an inability ttake oral or enteral medication via a feeding tube or a requirement for IV alimentation, or active peptic ulcer disease
• *Nother 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 nanticipated need for major surgical procedures during study
• At least 14 days since prior radiotherapy
• Nprior surgical procedure affecting absorption
• Nprior chronic, systemic corticosteroids or other immunosuppressive agent, except corticosteroids equivalent tprednisone ≤ 20 mg daily
  • Must have been on a stable dosage regimen for ≥ 4 weeks
  • Topical and inhaled corticosteroids allowed
• Nprior mTOR inhibitor therapy (i.e., rapamycin, everolimus, or temsirolimus)
• Nconcurrent immunization with attenuated live vaccines
• Nconcurrent antiretroviral therapy for HIV-positive patients
• Nother concurrent investigational therapy
• Nother concurrent anticancer agents