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

This study has been terminated.
  1. Lower accrual due to new less extensive suregery techniques.
  2. Patients exposed to asbestos increases in age leading to a lower accrual rate.
ClinicalTrials.gov Identifier:
First Posted: June 8, 2006
Last Update Posted: March 11, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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.

Condition Intervention Phase
Malignant Mesothelioma Drug: Cisplatin Drug: Pemetrexed Procedure: Therapeutic conventional surgery Radiation: Radiotherapy Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial

Resource links provided by NLM:

Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Complete macroscopic resection (part 1) [ Time Frame: After surgery (15 weeks after trial registration) ]
  • Loco-regional relapse-free survival (part 2) [ Time Frame: From surgery until the first occurrence of loco-regional relapse ]

Secondary Outcome Measures:
  • Response to neoadjuvant therapy (part 1) [ Time Frame: Every 6 months in the follow-up until death for a maximum of 5 years ]
  • Adverse drug reaction to neoadjuvant therapy (part 1) [ Time Frame: According to CTCAE ]
  • Operability (part 1) [ Time Frame: Proportion of patients remaining operable after completing chemotherapy (9 weeks after trial registration) ]
  • Surgical complications (part 1) [ Time Frame: Within 3 month after surgery ]
  • Reasons for non-randomization (part 1) [ Time Frame: Reasons for non-randomization include macroscopic incomplete resection, patients' refusal or patient can not be subjected to RT within 10 weeks after surgery. ]
  • Relapse-free or progression-free survival (part 1) [ Time Frame: From registration until progression/relapse (loco-regional or distant) or death ]
  • Adverse reaction to postoperative radiotherapy (part 2) [ Time Frame: According to CTCAE ]
  • Late toxicity (part 2) [ Time Frame: Late toxicities occurring later than 6 weeks after the last RT fraction ]
  • Feasibility of postoperative radiotherapy (part 2) [ Time Frame: Proportion of patients receiving at least 90% of planned RT dose ]
  • Relapse-free survival (part 2) [ Time Frame: From registration until progression/relapse (loco-regional or distant) or death ]
  • Psychological distress (quality of life) (part 2) [ Time Frame: Until 22 weeks after treatment termination ]
  • Overall survival [ Time Frame: From registration until death for all registered patients, and from randomization to death for all randomized patients. ]

Enrollment: 153
Study Start Date: November 2005
Estimated Study Completion Date: June 2018
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: No radiotherapy 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
Experimental: Radiotherapy 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.

Detailed Description:



  • 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 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.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00334594

Universitaetsklinikum Freiburg
Freiburg, Germany, D-79106
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Basel, Switzerland, CH-4031
Spital Tiefenau
Bern 4, Switzerland, 3004
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Olten
Olten, Switzerland, CH-4600
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
SpitalSTS AG Simmental-Thun-Saanenland
Thun, Switzerland, 3600
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Study Chair: Rolf A. Stahel, Prof UniversitaetsSpital Zuerich
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00334594     History of Changes
Other Study ID Numbers: SAKK 17/04
2006-000445-19 ( EudraCT Number )
LILLY-SAKK-17/04 ( Other Identifier: SAKK )
First Submitted: June 7, 2006
First Posted: June 8, 2006
Last Update Posted: March 11, 2015
Last Verified: March 2015

Keywords provided by Swiss Group for Clinical Cancer Research:
epithelial mesothelioma
sarcomatous mesothelioma
stage IA malignant mesothelioma
stage IB malignant mesothelioma
stage II malignant mesothelioma
stage III malignant mesothelioma

Additional relevant MeSH terms:
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors