Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial
- 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.
- 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
- 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
- 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
- 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
After completion of study treatment, patients are followed periodically for up to 5 years
PROJECTED ACCRUAL: A total of 155 patients will be accrued for this study.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete macroscopic resection (part 1)
After surgery (15 weeks after trial registration)
Rolf A. Stahel, Prof