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.
|First Received Date||October 8, 2008|
|Last Changed Date||January 10, 2017|
|Start Date||December 2008|
|Actual Primary Completion Date||April 2014|
|Primary Outcome Measures||
Progression-Free Survival [Time Frame: Every 8 weeks until disease progression, up to 3 years.]
|Secondary Outcome Measures||
Response [Time Frame: Every 8 weeks until disease progression, up to 3 years.]
Overall Survival [Time Frame: Every 8 weeks until disease progression, up to 3 years.]
Frequency and Severity of Toxicities [Time Frame: 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.]
|Study Arms / Comparison Groups||1 / 0|
- To determine the 4-month progression-free survival in patients with unresectable malignant pleural mesothelioma treated with everolimus.
- 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.
|Ages||18 Years - 120 Years|
|Accepts Healthy Volunteers||No|
- 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
- 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
|Sponsor||Southwest Oncology Group|
|Verification Date||January 2017|