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

NCT ID: NCT00334594

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-14
• Study Completion Date: 2018-01-23

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.

Conditions

Malignant Mesothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No radiotherapy

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Cisplatin 75 mg/m2 i.v. over approximately 2 hours on day 1 every 21 days

Pemetrexed

Intervention Type: DRUG

Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 every 21 days

Therapeutic conventional surgery

Intervention Type: PROCEDURE

Extrapleural pneumonectomy

Radiotherapy

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Cisplatin 75 mg/m2 i.v. over approximately 2 hours on day 1 every 21 days

Pemetrexed

Intervention Type: DRUG

Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 every 21 days

Therapeutic conventional surgery

Intervention Type: PROCEDURE

Extrapleural pneumonectomy

Radiotherapy

Intervention Type: RADIATION

CTV1 will receive 45 or 46 Gy. CTV2 will be treated up to a total dose of 55,9 to 56,2 Gy.

Interventions

Cisplatin

Cisplatin 75 mg/m2 i.v. over approximately 2 hours on day 1 every 21 days

Intervention Type: DRUG

Pemetrexed

Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 every 21 days

Intervention Type: DRUG

Therapeutic conventional surgery

Extrapleural pneumonectomy

Intervention Type: PROCEDURE

Radiotherapy

CTV1 will receive 45 or 46 Gy. CTV2 will be treated up to a total dose of 55,9 to 56,2 Gy.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rolf A. Stahel, Prof

Role: STUDY_CHAIR

UniversitaetsSpital Zuerich

Locations

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Spital Tiefenau

Bern, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

SpitalSTS AG Simmental-Thun-Saanenland

Thun, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Germany; Switzerland

References

Stahel RA, Riesterer O, Xyrafas A, Opitz I, Beyeler M, Ochsenbein A, Fruh M, Cathomas R, Nackaerts K, Peters S, Mamot C, Zippelius A, Mordasini C, Caspar CB, Eckhardt K, Schmid RA, Aebersold DM, Gautschi O, Nagel W, Topfer M, Krayenbuehl J, Ribi K, Ciernik IF, Weder W. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. Lancet Oncol. 2015 Dec;16(16):1651-8. doi: 10.1016/S1470-2045(15)00208-9. Epub 2015 Nov 2.

Reference Type: RESULT

PMID: 26538423 (View on PubMed)

Other Identifiers

SWS-SAKK-17/04

Identifier Type: -

Identifier Source: secondary_id

EU-20615

Identifier Type: -

Identifier Source: secondary_id

2006-000445-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LILLY-SAKK-17/04

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000481153

Identifier Type: -

Identifier Source: secondary_id

SAKK 17/04

Identifier Type: -

Identifier Source: org_study_id