Pemetrexed Disodium/Observation in Treating Patients W/ Malignant Pleural Mesothelioma w/Out Progressive Disease After 1st Line Chemotherapy

OBJECTIVES:

Primary

• 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

• To determine the overall survival of patients treated with this regimen versus observation.
• To evaluate the frequency of responses in patients treated with this regimen.
• To assess the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to first-line chemotherapy regimen (cisplatin/pemetrexed disodium vs carboplatin/pemetrexed disodium), histologic subtype (epithelioid vs other) and number of courses received (< 6 vs 6).

• 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.

Inclusion criteria

• Histologically confirmed malignant pleural mesothelioma meeting 1 of the following cell types:

• Epithelial
• Sarcomatoid
• Mixed type

• Histologically documented malignant pleural mesothelioma, epithelial, sarcomatoid or mixed type, not amenable to surgical resection
• Prior treatment
• Currently receiving first-line treatment with pemetrexed + platinum; patients are to be registered to Cancer and Leukemia Group B (CALGB) 30901 no later than the last day of cycle 4 of first line therapy
• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) are acceptable; prior intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy
• Prior surgical treatment is allowed
• Prior radiation therapy is allowed

• Non-pregnant and non-nursing; women of child bearing potential and men must agree to use an appropriate method of birth control throughout their participation in this study; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives (Norplant), or double barrier methods (diaphragm plus condom)
• RANDOMIZATION ELIGIBILITY CRITERIA
• Patients with complete response, partial response, or stable disease following 4, 5 or 6 cycles of first-line chemotherapy with pemetrexed AND either cisplatin or carboplatin; a maximum of 6 cycles of chemotherapy may have been given
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Granulocytes >= 1,500/ul
• Platelet count >= 100,000/ul
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 x ULN
• Calculated creatinine clearance >= 45 ml/min
• 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 within 9 weeks following day 1 of cycle 4 of first-line treatment
• No clinically significant pleural or peritoneal effusions that cannot be adequately managed by drainage before or during 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

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 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