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

NCT00334594 | Completed Phase 2

• 6 other identifiers: SAKK 17/04SWS-SAKK-17/04EU-206152006-000445-19LILLY-SAKK-17/04CDR0000481153
• Study Type: interventional
• Target: 153
• Locations: 2 countries
• Sites: 13

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.

Conditions

Malignant Mesothelioma

Keywords

epithelial mesothelioma; sarcomatous mesothelioma; stage IA malignant mesothelioma; stage IB malignant mesothelioma; stage II malignant mesothelioma; stage III malignant mesothelioma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• Response to neoadjuvant therapy (part 1)

  Every 6 months in the follow-up until death for a maximum of 5 years

• Adverse drug reaction to neoadjuvant therapy (part 1)

  According to CTCAE

• 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

• 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.

Study Arms (2)

No radiotherapy

ACTIVE COMPARATOR

Drug: Cisplatin; Drug: Pemetrexed; Procedure: Therapeutic conventional surgery

Radiotherapy

EXPERIMENTAL

Drug: Cisplatin; Drug: Pemetrexed; Procedure: Therapeutic conventional surgery; Radiation: Radiotherapy

Interventions

Cisplatin DRUG

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

No radiotherapy; Radiotherapy

Pemetrexed DRUG

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

No radiotherapy; Radiotherapy

Therapeutic conventional surgery PROCEDURE

Extrapleural pneumonectomy

No radiotherapy; Radiotherapy

Radiotherapy RADIATION

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

Radiotherapy

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (13)

Universitaetsklinikum Freiburg

Freiburg im Breisgau, D-79106, Germany

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Spital Tiefenau

Bern, 3004, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 26538423 RESULT

MeSH Terms

Conditions

Mesothelioma, Malignant; Solitary Fibrous Tumor, Pleural

Interventions

Cisplatin; Pemetrexed; Radiotherapy

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Solitary Fibrous Tumors; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Therapeutics

Study Officials

• Rolf A. Stahel, Prof

  UniversitaetsSpital Zuerich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2006
• First Posted: June 8, 2006
• Study Start: November 14, 2005
• Primary Completion: March 26, 2014
• Study Completion: January 23, 2018
• Last Updated: May 15, 2019

Record last verified: 2019-05

Locations

CH (12); DE (1)