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

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. Identifier: NCT00334594
Recruitment Status : Completed
First Posted : June 8, 2006
Last Update Posted : May 15, 2019
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief 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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
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
Actual Study Start Date : November 14, 2005
Actual Primary Completion Date : March 26, 2014
Actual Study Completion Date : January 23, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
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.

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

Secondary Outcome Measures :
  1. Response to neoadjuvant therapy (part 1) [ Time Frame: Every 6 months in the follow-up until death for a maximum of 5 years ]
  2. Adverse drug reaction to neoadjuvant therapy (part 1) [ Time Frame: According to CTCAE ]
  3. Operability (part 1) [ Time Frame: Proportion of patients remaining operable after completing chemotherapy (9 weeks after trial registration) ]
  4. Surgical complications (part 1) [ Time Frame: Within 3 month after surgery ]
  5. 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. ]
  6. Relapse-free or progression-free survival (part 1) [ Time Frame: From registration until progression/relapse (loco-regional or distant) or death ]
  7. Adverse reaction to postoperative radiotherapy (part 2) [ Time Frame: According to CTCAE ]
  8. Late toxicity (part 2) [ Time Frame: Late toxicities occurring later than 6 weeks after the last RT fraction ]
  9. Feasibility of postoperative radiotherapy (part 2) [ Time Frame: Proportion of patients receiving at least 90% of planned RT dose ]
  10. Relapse-free survival (part 2) [ Time Frame: From registration until progression/relapse (loco-regional or distant) or death ]
  11. Psychological distress (quality of life) (part 2) [ Time Frame: Until 22 weeks after treatment termination ]
  12. Overall survival [ Time Frame: From registration until death for all registered patients, and from randomization to death for all randomized patients. ]

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.

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
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

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 identifier (NCT number): NCT00334594

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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
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Study Chair: Rolf A. Stahel, Prof UniversitaetsSpital Zuerich
Publications of Results:
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Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT00334594    
Other Study ID Numbers: SAKK 17/04
2006-000445-19 ( EudraCT Number )
LILLY-SAKK-17/04 ( Other Identifier: SAKK )
First Posted: June 8, 2006    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
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:
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Mesothelioma, Malignant
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors