Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial
18 Years
69 Years
Both
Malignant Mesothelioma
Trial Information
Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed malignant pleural mesothelioma
- T1-3, N0-2, M0 disease according to International Mesothelioma Interest Group
staging system
- No obvious invasion of mediastinal structures by CT scan (e.g., heart, aorta, spine,
esophagus)
- No obvious widespread chest wall invasion
- Resectable chest wall lesions allowed
PATIENT CHARACTERISTICS:
- WHO performance score 0-1
- Fit for neoadjuvant therapy, surgery, and postoperative radiotherapy
- Creatinine clearance > 60 mL/min
- Hemoglobin ≥ 10.0 g/dL
- WBC ≥ 3,500/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 12 months
after completion of study treatment
- FEV_1 ≥ 40% of predicted based on spirometry and lung perfusion scan, if necessary
- No serious underlying medical condition that would preclude study requirements (e.g.,
active autoimmune disease or uncontrolled diabetes)
- No known hypersensitivity against pemetrexed disodium, cisplatin, or other
platinum-containing substances or any other components used for the preparation of
the drugs
- No restricted power of hearing (especially in the upper frequency range)
- No acute infections
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy
- No treatment on another clinical trial within the past 30 days
- No prior pleurectomy or lung resection
- No prior radiotherapy of the lower neck, thorax, or upper abdomen
- No aspirin, cyclooxygenase-2 inhibitors, or nonsteroidal anti-inflammatory agents for
5 days prior to, during, and for 2 days after pemetrexed disodium administration
- No other concurrent experimental drugs or anticancer therapy
- No concurrent drugs that would contraindicate study drugs
- No concurrent vaccination against yellow fever
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete macroscopic resection (part 1)
Outcome Time Frame:
After surgery (15 weeks after trial registration)
Safety Issue:
No
Principal Investigator
Rolf A. Stahel, Prof
Investigator Role:
Study Chair
Investigator Affiliation:
UniversitaetsSpital Zuerich
Authority:
Switzerland: Swissmedic
Study ID:
SAKK 17/04
NCT ID:
NCT00334594
Start Date:
November 2005
Completion Date:
June 2018
Related Keywords:
- Malignant Mesothelioma
- epithelial mesothelioma
- sarcomatous mesothelioma
- stage IA malignant mesothelioma
- stage IB malignant mesothelioma
- stage II malignant mesothelioma
- stage III malignant mesothelioma
- Mesothelioma
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