Pemetrexed Disodium and Cisplatin Followed By Surgery and Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and cisplatin followed by surgery and radiation therapy works in treating patients with malignant pleural mesothelioma.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of neoadjuvant chemotherapy comprising pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and high-dose postoperative 3D-conformal radiotherapy, in terms of 90-day progression-free survival, in patients with malignant pleural mesothelioma. Secondary Determine the toxicity of this regimen in these patients. Determine progression-free survival and overall survival of patients treated with this regimen. OUTLINE: This is a non-randomized, multicenter study. Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated 3 weeks after completion of neoadjuvant chemotherapy. Patients without disease progression proceed to surgery. Extrapleural pneumonectomy: Within 21-56 days after completion of neoadjuvant chemotherapy, patients undergo extrapleural pneumonectomy. Patients are evaluated 30 days after surgery. Patients without disease progression undergo high-dose 3D-conformal radiotherapy. High-dose 3D-conformal radiotherapy: Beginning 30-84 days after surgery, patients undergo high-dose 3D-conformal radiotherapy daily for 30 days. After completion of study treatment, patients are followed on days 42 and 90, every 3 months for 1 year, and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

Official Title
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A Phase II Feasibility Trial of Induction Chemotherapy Followed by Extrapleural Pneumonectomy and Postoperative Radiotherapy in Patients With Malignant Pleural Mesothelioma

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: cisplatin
* Drug: pemetrexed disodium
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant pleural mesothelioma All subtypes allowed T1-3, N0-1, M0 disease No N2 or N3 involvement confirmed by mediastinoscopy within 21 days before study entry No clinical invasion of mediastinal structures (e.g., heart, aorta, spine, esophagus) No wide-spread chest wall invasion except focal chest wall lesions No clinical or radiological evidence of shrinking hemithorax No clinically significant third-space fluid (e.g., pleural effusions or ascites) that cannot be managed with thoracentesis or pleurodesis PATIENT CHARACTERISTICS: Age Under 70 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic WBC > 3,500/mm^3 Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Hemoglobin ≥ 11 g/dL Hepatic AST and ALT < 1.5 times upper limit of normal (ULN) Bilirubin < 1.5 times ULN Alkaline phosphatase < 1.5 times ULN Renal Creatinine clearance ≥ 60 mL/min Acceptable (predicted) post-radiotherapy renal function by semiquantitative isotope renography, with a relative contribution of the contralateral kidney of ≥ 40% Pulmonary See Disease Characteristics Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment Deemed to be fit enough to undergo study treatment No preexisting sensory neurotoxicity > grade 1 No uncontrolled infection No prior or concurrent melanoma, breast cancer, or hypernephroma No other malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer No psychological, familial, sociological, or geographical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy No concurrent routine use of colony-stimulating factors during neoadjuvant chemotherapy Concurrent secondary prophylactic use allowed during neoadjuvant chemotherapy No concurrent secondary prophylactic use of colony-stimulating factors during post-operative radiotherapy Chemotherapy No prior chemotherapy for mesothelioma Endocrine therapy No concurrent hormonal cancer therapy Radiotherapy No prior radiotherapy to the lower neck, thorax, or upper abdomen Surgery See Disease Characteristics Other No other concurrent anticancer therapy No other concurrent experimental medications No nonsteroidal anti-inflammatory drugs or salicylates for 2 days before, during, and 2 days after administration of neoadjuvant chemotherapy (5 days before and 2 days after for drugs with a long half-life [e.g., naproxen, piroxicam, diflunisal, or nabumetone])

Ages Eligible for Study
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Maximum Age: 69 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: pemetrexed disodium|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility in terms of 90-day progression-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  |  | 
| Progression-free survival |  |  | 
| Overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epithelial mesothelioma, sarcomatous mesothelioma, localized malignant mesothelioma, recurrent malignant mesothelioma