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.
)
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00334594
First received: June 7, 2006
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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) ] [ Designated as safety issue: No ]
  • Loco-regional relapse-free survival (part 2) [ Time Frame: From surgery until the first occurrence of loco-regional relapse ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • Adverse drug reaction to neoadjuvant therapy (part 1) [ Time Frame: According to CTCAE ] [ Designated as safety issue: Yes ]
  • Operability (part 1) [ Time Frame: Proportion of patients remaining operable after completing chemotherapy (9 weeks after trial registration) ] [ Designated as safety issue: No ]
  • Surgical complications (part 1) [ Time Frame: Within 3 month after surgery ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Relapse-free or progression-free survival (part 1) [ Time Frame: From registration until progression/relapse (loco-regional or distant) or death ] [ Designated as safety issue: No ]
  • Adverse reaction to postoperative radiotherapy (part 2) [ Time Frame: According to CTCAE ] [ Designated as safety issue: Yes ]
  • Late toxicity (part 2) [ Time Frame: Late toxicities occurring later than 6 weeks after the last RT fraction ] [ Designated as safety issue: Yes ]
  • Feasibility of postoperative radiotherapy (part 2) [ Time Frame: Proportion of patients receiving at least 90% of planned RT dose ] [ Designated as safety issue: No ]
  • Relapse-free survival (part 2) [ Time Frame: From registration until progression/relapse (loco-regional or distant) or death ] [ Designated as safety issue: No ]
  • Psychological distress (quality of life) (part 2) [ Time Frame: Until 22 weeks after treatment termination ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From registration until death for all registered patients, and from randomization to death for all randomized patients. ] [ Designated as safety issue: No ]

Enrollment: 153
Study Start Date: November 2005
Estimated Study Completion Date: June 2018
Estimated 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:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334594

Locations
Germany
Universitaetsklinikum Freiburg
Freiburg, Germany, D-79106
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Inselspital Bern
Bern, Switzerland, CH-3010
Spital Tiefenau
Bern 4, Switzerland, 3004
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
Investigators
Study Chair: Rolf A. Stahel, Prof UniversitaetsSpital Zuerich
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00334594     History of Changes
Other Study ID Numbers: SAKK 17/04, SWS-SAKK-17/04, EU-20615, EUDRACT-2006-000445-19, LILLY-SAKK-17/04, CDR0000481153
Study First Received: June 7, 2006
Last Updated: November 28, 2012
Health Authority: Switzerland: Swissmedic

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:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 16, 2014