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

Sponsor:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00334594

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 disodium Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: quality-of-life assessment Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
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:

MedlinePlus related topics: Cancer Mesothelioma Surgery

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete macroscopic resection (part 1) [ Designated as safety issue: No ]
Loco-regional relapse-free survival (part 2) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response to neoadjuvant therapy (part 1) [ Designated as safety issue: No ]
Adverse drug reaction to neoadjuvant therapy (part 1) [ Designated as safety issue: Yes ]
Operability (part 1) [ Designated as safety issue: No ]
Surgical complications (part 1) [ Designated as safety issue: No ]
Reasons for non-randomization (part 1) [ Designated as safety issue: No ]
Relapse-free or progression-free survival (part 1) [ Designated as safety issue: No ]
Adverse reaction to postoperative radiotherapy (part 2) [ Designated as safety issue: Yes ]
Late toxicity (part 2) [ Designated as safety issue: Yes ]
Feasibility of postoperative radiotherapy (part 2) [ Designated as safety issue: No ]
Relapse-free survival (part 2) [ Designated as safety issue: No ]
Psychological distress (quality of life) (part 2) [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	155
Study Start Date:	November 2005
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

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	Recruiting
Freiburg, Germany, D-79106
Contact: Contact Person 49-761-270-2455
Switzerland
Centre Hospitalier Universitaire Vaudois	Recruiting
Lausanne, Switzerland, CH-1011
Contact: Contact Person 41-21-314-4604
FMH Onkologie/Haematologie	Recruiting
Rheinfelden, Switzerland, 4310
Contact: Contact Person 41-61-836-9393
Inselspital Bern	Recruiting
Bern, Switzerland, CH-3010
Contact: Contact Person 41-31-632-8169
Kantonsspital - St. Gallen	Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Contact Person 41-71-494-1068
Kantonsspital Baden	Recruiting
Baden, Switzerland, CH-5404
Contact: Contact Person 41-56-486-2511
Universitaetsspital-Basel	Recruiting
Basel, Switzerland, CH-4031
Contact: Contact Person 41-61-265-5075
Kantonsspital Graubuenden	Recruiting
Chur, Switzerland, CH-7000
Contact: Contact Person 41-81-256-6111
Kantonsspital Olten	Recruiting
Olten, Switzerland, CH-4600
Contact: Contact Person 41-62-311-4241
Regionalspital	Recruiting
Thun, Switzerland, 3600
Contact: Contact Person 41-33-226-2645
Spital Tiefenau	Recruiting
Bern 4, Switzerland, 3004
Contact: Contact Person 41-31-308-8111
UniversitaetsSpital Zuerich	Recruiting
Zurich, Switzerland, CH-8091
Contact: Rolf A. Stahel, MD 41-1-634-2871 rolf.stahel@usz.ch
Kantonsspital Bruderholz	Recruiting
Bruderholz, Switzerland, CH-4101
Contact: Contact Person 41-61-436-3636

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:

Rolf A. Stahel, MD

UniversitaetsSpital Zuerich

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000481153, SWS-SAKK-17/04, EU-20615, EUDRACT-2006-000445-19, LILLY-SAKK-17/04
Study First Received:	June 7, 2006
Last Updated:	October 30, 2009
ClinicalTrials.gov Identifier:	NCT00334594 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

advanced malignant mesothelioma
epithelial mesothelioma
sarcomatous mesothelioma
localized malignant mesothelioma

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Neoplasms, Mesothelial
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Folic Acid Antagonists

Pharmacologic Actions
Pemetrexed
Neoplasms
Cisplatin
Radiation-Sensitizing Agents
Therapeutic Uses
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009