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

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Malignant Mesothelioma

Treatments

Drug: everolimus

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00770120

S0722 (Other Identifier)

CDR0000616162

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

61 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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