NCT00334594

Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 153 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years – 69 Years
• Healthy volunteers: Not accepted

Summary

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. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium together with cisplatin followed by surgery with or without radiation therapy works in treating patients with malignant pleural mesothelioma.

Detailed description

OBJECTIVES: Primary * Evaluate the short-term outcomes and feasibility of neoadjuvant therapy with pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy in patients with malignant pleural mesothelioma. * Evaluate the long-term outcomes and feasibility of postoperative hemithoracic radiotherapy in patients with R0 or R1 resection. Secondary * Determine the quality of life of these patients. * Identify predictive and prognostic markers in these patients. * Determine relapse-free or progression-free survival and overall survival of these patients. * Collect tissue and blood from these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, histology (sarcomatous or other vs epithelial or mixed histology), nodal status (N0-1 vs N2), and extent of disease (T1-2 vs T3). * Part 1 (neoadjuvant therapy and surgery): Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 8 weeks after completion of neoadjuvant therapy, patients without progressive disease undergo extrapleural pneumonectomy. * Part 2 : Patients achieving R0 or R1 resection proceed to part 2 of study treatment and are randomized to 1 of 2 treatment arms. Patients with R2 resection, disease progression, or symptomatic deterioration after treatment in part 1 are taken off study. * Arm I (no postoperative radiotherapy): Patients do not undergo radiotherapy. Quality of life is assessed at baseline and at 6, 10, 16, and 22 weeks after randomization. * Arm II (postoperative radiotherapy): Beginning within 10 weeks after surgery, patients undergo radiotherapy to the hemithoracic region 5 days a week for approximately 5 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at 4, 8, 14, and 20 weeks after initiation of radiotherapy. Patients undergo blood and tissue collection at registration and surgery for laboratory and biomarker analysis. After completion of study treatment, patients are followed periodically for up to 5 years after surgery. PROJECTED ACCRUAL: A total of 155 patients will be accrued for this study.

Conditions

• Malignant Mesothelioma

Interventions

Type	Name	Description
DRUG	Cisplatin	Cisplatin 75 mg/m2 i.v. over approximately 2 hours on day 1 every 21 days
DRUG	Pemetrexed	Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 every 21 days
PROCEDURE	Therapeutic conventional surgery	Extrapleural pneumonectomy
RADIATION	Radiotherapy	CTV1 will receive 45 or 46 Gy. CTV2 will be treated up to a total dose of 55,9 to 56,2 Gy.

Timeline

• Start date: 2005-11-14
• Primary completion: 2014-03-26
• Completion: 2018-01-23
• First posted: 2006-06-08
• Last updated: 2019-05-15

Locations

13 sites across 2 countries: Germany, Switzerland