Phase II Trial of Neo-Adjuvant Pemetrexed Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma

Study Overview
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Brief Summary
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This study aims to determine how successful the chemotherapy regimen of Pemetrexed plus cisplatin before surgery is at killing all the tumor so that none is left at the time of surgery. Following surgery, all eligible patients will receive radiation to the chest. How patients respond, whether the cancer returns and if so, where, will also be monitored.

Official Title
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A Multicenter Phase II Trial of Neo-Adjuvant Pemetrexed (Alimta) Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma

Conditions
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Pleural Neoplasms

Intervention / Treatment
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* Drug: pemetrexed
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be clinically staged using AJCC/UICC TNM staging criteria. Eligible stages: Patients must be M0 Patients with T1, T2, and T3 disease (without cardiac involvement) are eligible (T status can be established clinically and radiologically or at exploratory thoracotomy without surgical resection Patients with N0, N1,or N2 disease are eligible Performance status of 0 to 1 on the ECOG performance status schedule. No prior systemic chemotherapy and no prior intracavitary cytotoxic drugs or immunomodulators, unless given for the purpose of chemical pleurodesis No previous radiation therapy Estimated life expectancy of at least 12 weeks Exclusion Criteria: Patients will be excluded if they meet ANY of the following criteria: Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry Have previously completed or withdrawn from this study or any other study investigating pemetrexed Pregnancy or breast-feeding Serious concomitant systemic disorders (i.e. active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study Second active primary malignancy (except in situ carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin, low grade (Gleason score less than or equal to 6), localized adenocarcinoma of the prostate or other malignancy treated at least 2 years previously with no evidence of recurrence

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>chemotherapy, surgery then chest radiation x 54 gray (Gy) | Drug: pemetrexed<br>* 500 mg/m2, intravenous (IV), every 21 days x 4 cycles<br>* Other names: Alimta;Drug: cisplatin<br>* 75 mg/m2, intravenous (IV), every 21 days x 4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response | Number of participants with results of pathological review that indicated a complete response. Pathological complete response should be evaluated at the time of surgery (Extrapleural Pneumonectomy [EPP]). Resected tissue or pleural fluid should be sent for pathological and histological evaluation. | Surgery (at least 3 weeks post last dose of chemotherapy, up to a maximum interval of 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The 1 and 2 Year Disease-Free Survival Rate (Percentage) | Kaplan-Meier estimates of the percentage of participants still alive at 1-year and 2-years, based upon the total number of participants who had surgery. | 1 year and 2 years | 
| Overall Tumor Response | The frequency of best overall tumor response summarized by response category. The best (unconfirmed) response recorded from the start of chemotherapy treatment until disease progression/recurrence, start of any further anti-tumor therapy, or time of surgery whichever comes first. | baseline to measured progressive disease | 
| Time to Treatment Failure | Time to relapse (treatment failure) is measured in months and calculated as (Date of first surgery - Date of first relapse after surgery + 1)/(365.25/12). Time to relapse will be censored at the date of the last visit or start date of further anti-tumor therapy or intervention, whichever comes first. | baseline to stopping treatment | 
| Time to Progressive Disease | Number of months between the first dose date and the date of first disease progression or death as a result of any cause, whichever comes first. | baseline to measured progressive disease | 
| Overall Survival Time | Number of months between the first dose date and the date of death as a result of any cause. Overall survival time calculated as (Date of death - First dose date + 1)/(365.25/12). | baseline to date of death from any cause |