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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00334594
Other study ID # SAKK 17/04
Secondary ID SWS-SAKK-17/04EU
Status Completed
Phase Phase 2
First received
Last updated
Start date November 14, 2005
Est. completion date January 23, 2018

Study information

Verified date May 2019
Source Swiss Group for Clinical Cancer Research
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 153
Est. completion date January 23, 2018
Est. primary completion date March 26, 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years to 69 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Germany Universitaetsklinikum Freiburg Freiburg
Switzerland Kantonsspital Aarau Aarau
Switzerland Kantonsspital Baden Baden
Switzerland Universitaetsspital-Basel Basel
Switzerland Inselspital Bern Bern
Switzerland Spital Tiefenau Bern 4
Switzerland Kantonsspital Bruderholz Bruderholz
Switzerland Kantonsspital Graubuenden Chur
Switzerland Centre Hospitalier Universitaire Vaudois Lausanne
Switzerland Kantonsspital Olten Olten
Switzerland Kantonsspital - St. Gallen St. Gallen
Switzerland SpitalSTS AG Simmental-Thun-Saanenland Thun
Switzerland UniversitaetsSpital Zuerich Zurich

Sponsors (1)

Lead Sponsor Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Germany,  Switzerland, 

References & Publications (1)

Stahel RA, Riesterer O, Xyrafas A, Opitz I, Beyeler M, Ochsenbein A, Früh 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, Töpfer M, Krayenbuehl J, Ribi K, Cierni — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Complete macroscopic resection (part 1) After surgery (15 weeks after trial registration)
Primary Loco-regional relapse-free survival (part 2) From surgery until the first occurrence of loco-regional relapse
Secondary Response to neoadjuvant therapy (part 1) Every 6 months in the follow-up until death for a maximum of 5 years
Secondary Adverse drug reaction to neoadjuvant therapy (part 1) According to CTCAE
Secondary Operability (part 1) Proportion of patients remaining operable after completing chemotherapy (9 weeks after trial registration)
Secondary Surgical complications (part 1) Within 3 month after surgery
Secondary 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.
Secondary Relapse-free or progression-free survival (part 1) From registration until progression/relapse (loco-regional or distant) or death
Secondary Adverse reaction to postoperative radiotherapy (part 2) According to CTCAE
Secondary Late toxicity (part 2) Late toxicities occurring later than 6 weeks after the last RT fraction
Secondary Feasibility of postoperative radiotherapy (part 2) Proportion of patients receiving at least 90% of planned RT dose
Secondary Relapse-free survival (part 2) From registration until progression/relapse (loco-regional or distant) or death
Secondary Psychological distress (quality of life) (part 2) Until 22 weeks after treatment termination
Secondary Overall survival From registration until death for all registered patients, and from randomization to death for all randomized patients.
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