Primary Outcome Measures:
- Progression-free survival: To determine if maintenance therapy with pemetrexed disodium versus observation improves progression-free survival of patients with malignant pleural mesothelioma who have at least stable disease after completion of first-line therapy comprising pemetrexed disodium with cisplatin or carboplatin.
Secondary Outcome Measures:
- Overall survival: To determine the overall survival of patients treated with this regimen versus observation.
- Frequency of responses: To evaluate the frequency of responses in patients treated with this regimen.
- Toxicity: To assess the toxicity of this regimen in these patients.
Detailed Description:
Outline: This is a multicenter study. Patients are stratified according to first-line chemotherapy regimen (cisplatin/pemetrexed disodium vs carboplatin/pemetrexed disodium) and histologic subtype (epithelioid vs other).
- Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo observation until disease progression. After completion of study therapy, patients are followed up every 6 months for 3 years.
Criteria
- Disease Characteristics:
-
- Histologically confirmed malignant pleural mesothelioma meeting 1 of the following cell types:
- Epithelial
- Sarcomatoid
- Mixed type
- Disease not amenable to surgery
- Must be enrolled on imaging protocol CALGB-580903
- Complete response, partial response, or stable disease after completion of 4 courses of first-line chemotherapy comprising pemetrexed disodium AND cisplatin or carboplatin
- Study therapy will begin ≥ 3 weeks and ≤ 6 weeks after the completion of course 4
- No clinically significant pleural or peritoneal effusions that cannot be adequately managed by drainage before or during pemetrexed disodium
- Prior/Concurrent Therapy:
-
- See Disease Characteristics
- Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed
- Prior intrapleural cytotoxic chemotherapy not considered systemic chemotherapy
- Prior surgery allowed
- Prior radiotherapy allowed
- No concurrent palliative radiotherapy
- No NSAIDS for 5 days before, during, or 2 days after study therapy
- No concurrent hormones or other chemotherapeutic agents except for the following:
- Steroids for adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
- Intermittent use of dexamethasone as an antiemetic or premedication for pemetrexed disodium
- Patient Characteristics:
-
- ECOG performance status of 0-1
- Life expectancy ≥ 12 weeks
- Granulocytes ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 2 times ULN
Creatinine clearance ≥ 45 mL/min - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No psychiatric illness that would prevent the patient from giving informed consent
- No second malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix unless curatively treated with no evidence of active disease for ≥ 5 years
- No medical conditions that, in the opinion of the treating physician, would make study treatment unreasonably hazardous for the patient including, but not limited to, the following:
- Ongoing or active infection such as HIV positivity
- Inability to take oral medications
- Psychiatric illness/social situations that would limit compliance with study requirements
