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

Study Overview
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Brief Summary
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RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This randomized phase II trial is studying how well pemetrexed disodium or observation works in treating patients with malignant pleural mesothelioma without progressive disease after first-line chemotherapy.

Detailed Description
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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.

Official Title
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Randomized Phase II Study of Maintenance Pemetrexed Versus Observation for Patients With Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: pemetrexed disodium
* Other: clinical observation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: pemetrexed disodium<br>* Given IV<br>* Other names: 150399-23-8;|
| Active Comparator: Arm II<br>Patients undergo observation until disease progression. | Other: clinical observation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. | Baseline up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. | Baseline up to 3 years | 
| Response Rate | The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test | Up to 3 years | 
| Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) | The number of patients reporting grade 3 or higher adverse events considered at least possibly related to study treatment as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report. | Baseline up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epithelial mesothelioma, sarcomatous mesothelioma, stage II malignant mesothelioma, stage III malignant mesothelioma, stage IV malignant mesothelioma