Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma
- Conditions
- Malignant Mesothelioma
- Interventions
- Registration Number
- NCT00334594
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 153
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description No radiotherapy Cisplatin - Radiotherapy Cisplatin - Radiotherapy Pemetrexed - Radiotherapy Radiotherapy - No radiotherapy Therapeutic conventional surgery - Radiotherapy Therapeutic conventional surgery - No radiotherapy Pemetrexed -
- Primary Outcome Measures
Name Time Method Complete macroscopic resection (part 1) After surgery (15 weeks after trial registration) Loco-regional relapse-free survival (part 2) From surgery until the first occurrence of loco-regional relapse
- Secondary Outcome Measures
Name Time Method Response to neoadjuvant therapy (part 1) Every 6 months in the follow-up until death for a maximum of 5 years Operability (part 1) Proportion of patients remaining operable after completing chemotherapy (9 weeks after trial registration) Surgical complications (part 1) Within 3 month after surgery Relapse-free or progression-free survival (part 1) From registration until progression/relapse (loco-regional or distant) or death Adverse drug reaction to neoadjuvant therapy (part 1) According to CTCAE Adverse reaction to postoperative radiotherapy (part 2) According to CTCAE Late toxicity (part 2) Late toxicities occurring later than 6 weeks after the last RT fraction Psychological distress (quality of life) (part 2) Until 22 weeks after treatment termination Reasons for non-randomization (part 1) Reasons for non-randomization include macroscopic incomplete resection, patients' refusal or patient can not be subjected to RT within 10 weeks after surgery. Feasibility of postoperative radiotherapy (part 2) Proportion of patients receiving at least 90% of planned RT dose Relapse-free survival (part 2) From registration until progression/relapse (loco-regional or distant) or death Overall survival From registration until death for all registered patients, and from randomization to death for all randomized patients.
Trial Locations
- Locations (13)
Universitaetsspital-Basel
🇨ðŸ‡Basel, Switzerland
Inselspital Bern
🇨ðŸ‡Bern, Switzerland
Kantonsspital Graubuenden
🇨ðŸ‡Chur, Switzerland
SpitalSTS AG Simmental-Thun-Saanenland
🇨ðŸ‡Thun, Switzerland
Kantonsspital Bruderholz
🇨ðŸ‡Bruderholz, Switzerland
Kantonsspital Olten
🇨ðŸ‡Olten, Switzerland
UniversitaetsSpital Zuerich
🇨ðŸ‡Zurich, Switzerland
Kantonsspital Aarau
🇨ðŸ‡Aarau, Switzerland
Spital Tiefenau
🇨ðŸ‡Bern 4, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨ðŸ‡Lausanne, Switzerland
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Kantonsspital Baden
🇨ðŸ‡Baden, Switzerland
Kantonsspital - St. Gallen
🇨ðŸ‡St. Gallen, Switzerland