Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	18 to 69	Other, Pharmaceutical / Industry	SWS-SAKK-17/04 EU-20615, EUDRACT-2006-000445-19, LILLY-SAKK-17/04, NCT00334594

Objectives

Primary

1. 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.
2. Evaluate the long-term outcomes and feasibility of postoperative hemithoracic radiotherapy in patients with R0 or R1 resection.

Secondary

1. Determine the quality of life of these patients.
2. Identify predictive and prognostic markers in these patients.
3. Determine relapse-free or progression-free survival and overall survival of these patients.
4. Collect tissue and blood from these patients.

Entry 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

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

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
• FEV₁ ≥ 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

Expected Enrollment

A total of 155 patients will be accrued for this study.

Outcomes

Complete macroscopic resection (part 1)
Loco-regional relapse-free survival (part 2)

Response to neoadjuvant therapy (part 1)
Adverse drug reaction to neoadjuvant therapy (part 1)
Operability (part 1)
Surgical complications (part 1)
Reasons for non-randomization (part 1)
Relapse-free or progression-free survival (part 1)
Adverse reaction to postoperative radiotherapy (part 2)
Late toxicity (part 2)
Feasibility of postoperative radiotherapy (part 2)
Relapse-free survival (part 2)
Psychological distress (quality of life) (part 2)
Overall survival

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.

Trial Contact Information

Trial Lead Organizations

Swiss Group for Clinical Cancer Research

Rolf Stahel, MD, Protocol chair		Ph: 41-1-634-2871 Email: rolf.stahel@usz.ch

Germany
	Freiburg
	Universitaetsklinikum Freiburg
		Contact Person	Ph:  49-761-270-2455
Switzerland
	Baden
	Kantonsspital Baden
		Contact Person	Ph:  41-56-486-2511
	Basel
	Universitaetsspital-Basel
		Contact Person	Ph:  41-61-265-5075
	Bern
	Inselspital Bern
		Contact Person	Ph:  41-31-632-8169
	Bern 4
	Spital Tiefenau
		Contact Person	Ph:  41-31-308-8111
	Bruderholz
	Kantonsspital Bruderholz
		Contact Person	Ph:  41-61-436-3636
	Chur
	Kantonsspital Graubuenden
		Contact Person	Ph:  41-81-256-6111
	Lausanne
	Centre Hospitalier Universitaire Vaudois
		Contact Person	Ph:  41-21-314-4604
	Olten
	Kantonsspital Olten
		Contact Person	Ph:  41-62-311-4241
	Rheinfelden
	FMH Onkologie/Haematologie
		Contact Person	Ph:  41-61-836-9393
	St. Gallen
	Kantonsspital - St. Gallen
		Contact Person	Ph:  41-71-494-1068
	Thun
	Regionalspital
		Contact Person	Ph:  41-33-226-2645
	Zurich
	UniversitaetsSpital Zuerich
		Rolf Stahel, MD	Ph:  41-1-634-2871
			Email: rolf.stahel@usz.ch

Registry Information
Official Title		Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial
Trial Start Date		2005-11-11
Trial Completion Date		2012-12-30 (estimated)
Registered in ClinicalTrials.gov		NCT00334594
Date Submitted to PDQ		2006-04-13
Information Last Verified		2009-07-19

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