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
- Histologically confirmed malignant pleural mesothelioma
- 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
- Previous pulmonary embolism allowed provided the patient is on therapeutic low molecular weight heparin injections or warfarin AND nevidence of bleeding
- 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