Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma
This study is currently recruiting participants.
Verified June 2012 by Swiss Group for Clinical Cancer Research
Sponsor:
Swiss Group for Clinical Cancer Research
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00334594
First received: June 7, 2006
Last updated: June 29, 2012
Last verified: June 2012
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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 ]
| Estimated Enrollment: | 155 |
| Study Start Date: | November 2005 |
| Estimated Study Completion Date: | December 2017 |
| Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| No Intervention: 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
Contacts
| Contact: Rolf A. Stahel, Prof | +41 44 634 28 71 | rolf.stahel@usz.ch |
Locations
| Germany | |
| Universitaetsklinikum Freiburg | Recruiting |
| Freiburg, Germany, D-79106 | |
| Contact: Bernward Passlick, Prof +49-761-270-2455 passlick@ch11.ukl.uni-freiburg.de | |
| Principal Investigator: Bernward Passlick, Prof | |
| Switzerland | |
| Kantonsspital Aarau | Recruiting |
| Aarau, Switzerland, CH-5001 | |
| Contact: Christoph Mamot, MD +41 62 838 60 64 christoph.mamot@ksa.ch | |
| Principal Investigator: Christoph Mamot, MD | |
| Kantonsspital Baden | Recruiting |
| Baden, Switzerland, CH-5404 | |
| Contact: Clemens B. Caspar, MD 41-56-486-2511 clemens.caspar@ksb.ch | |
| Principal Investigator: Clemens B. Caspar, MD | |
| Universitaetsspital-Basel | Recruiting |
| Basel, Switzerland, CH-4031 | |
| Contact: Alfred Zippelius, Prof. 41-61-328-6016 azippelius@uhbs.ch | |
| Principal Investigator: Alfred Zippelius, Prof. | |
| Inselspital Bern | Recruiting |
| Bern, Switzerland, CH-3010 | |
| Contact: Adrian Ochsenbein, Prof. +41 31 632 81 69 adrian.ochsenbein@sec.insel.ch | |
| Principal Investigator: Adrian Ochsenbein, MD | |
| Spital Tiefenau | Recruiting |
| Bern 4, Switzerland, 3004 | |
| Contact: Carlo Mordasini, MD 41-31-308-8111 carlo.mordasini@spitalnetzbern.ch | |
| Principal Investigator: Carlo Mordasini, MD | |
| Kantonsspital Bruderholz | Recruiting |
| Bruderholz, Switzerland, CH-4101 | |
| Contact: Lorenz M. Jost, MD 41-61-436-3636 lorenz.jost@ksbh.ch | |
| Principal Investigator: Lorenz M. Jost, MD | |
| Kantonsspital Graubuenden | Recruiting |
| Chur, Switzerland, CH-7000 | |
| Contact: Roger von Moos, MD 41-81-256-6111 roger.vonmoos@ksgr.ch | |
| Principal Investigator: Roger von Moos, MD | |
| Centre Hospitalier Universitaire Vaudois | Recruiting |
| Lausanne, Switzerland, CH-1011 | |
| Contact: Solange Peters, MD 41-21-314-0343 solange.peters@chuv.ch | |
| Principal Investigator: Solange Peters, MD | |
| Kantonsspital Olten | Recruiting |
| Olten, Switzerland, CH-4600 | |
| Contact: Walter Mingrone, MD 41-62-311-4241 wmingrone_ol@spital.ktso.ch | |
| Principal Investigator: Walter Mingrone, MD | |
| Kantonsspital - St. Gallen | Recruiting |
| St. Gallen, Switzerland, CH-9007 | |
| Contact: Martin Früh, MD +41 71 494 10 68 martin.frueh@kssg.ch | |
| Principal Investigator: Martin Früh, MD | |
| SpitalSTS AG Simmental-Thun-Saanenland | Recruiting |
| Thun, Switzerland, 3600 | |
| Contact: Daniel Rauch +41 33 226 26 45 daniel.rauch@spitalstsag.ch | |
| Principal Investigator: Daniel Rauch, MD | |
| UniversitaetsSpital Zuerich | Recruiting |
| Zurich, Switzerland, CH-8091 | |
| Contact: Rolf A. Stahel, MD 41-1-634-2871 rolf.stahel@usz.ch | |
| Principal Investigator: Rolf A. Stahel, Prof | |
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: | June 29, 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 October 16, 2012
