Short Neoadjuvant Hemithoracic IMRT for MPM

NCT00797719 | Completed Phase 1 DMC

• 1 other identifier: UHN REB 08-0106-C
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Malignant pleural mesotheliomas (MPMs) are tumours associated with asbestos exposure involving the tissue lining surrounding the lung. Radiation therapy (RT) dramatically reduces the risk of tumour recurrence within the irradiated area (\>90%). But patients continue to succumb to MPMs due to the tumour spreading outside the chest cavity. This may be due to tumour cells inadvertently contaminating areas outside the chest cavity during surgery. The study will look at whether giving a short intense course of chest radiation just prior to surgery will sterilized these tumour cells and thus, avoid or reduce contamination of the areas outside the chest cavity. The investigators hypothesize that short neoadjuvant (pre-operative) hemithoracic RT, followed by immediate planned extrapleural pneumonectomy (EPP) (+/- adjuvant chemotherapy) will reduce the risk of intra-operative seeding and reduce the incidence of distant metastatic disease.

Conditions

Malignant Pleural Mesothelioma

Keywords

MPM; Short hemithoracic IMRT

Outcome Measures

Primary Outcomes (1)

• The primary outcome for the study will be the proportion of patients treated as per protocol without treatment related mortality.

  After completion of therapy: every 4 wks for 3 mos, then every 6 wks for 6 mos, then every 2 mos for 12 mos, then every 3 mos for 2 yrs, then every 6 mos for 5 years

Secondary Outcomes (1)

• To evaluate: acute and late morbidity related to treatment; local & distant recurrence, disease free & overall survival; identify factors/parameters associated with increased risk of treatment morbidity

  After completion of therapy: every 4 wks for 3 mos, then every 6 wks for 6 mos, then every 2 mos for 12 mos, then every 3 mos for 2 yrs, then every 6 mos for 5 years

Study Arms (1)

All

EXPERIMENTAL

This is a single arm study. All patients enrolled will be in this arm.

Other: Pre-op RT +/- chemotherapy

Interventions

Pre-op RT +/- chemotherapy OTHER

Patients on the study will receive IMRT for approximately 1 week of 5 daily treatments. Short pre-operative hemithoracic RT is a new technique. 1 week post-RT, they will proceed with an extrapleural pneumonectomy. If the mediastinal lymph nodes that are removed during surgery are positive for tumour cells, 3 cycles of chemotherapy, consisting of raltitrexed and cisplatin, will be given 6-12 weeks post-surgery.

All

Eligibility Criteria

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

You may qualify if:

• ECOG performance status of 0-2
• Good pulmonary function precluding radiation therapy (FEV\>1 L or \>40% predicted or DLCO \>45% predicted)
• Any patient wiht a new histological diagnosis of malignancy pleural mesothelioma (MPM). Sarcomatoid or biphasic histologies can be included but will be analyzed separately due to their poor prognosis
• Stage T1-2N0M0 based on conventional investigations and tests. Selected stage T3N0M0 may be included at the discretion of the surgeon if deemed resectable.
• Suitable for combined modality therapy
• Informed consent

You may not qualify if:

• Distant metastatic disease
• Previous thoracic irradiation
• Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus erythematosus (SLE), scleroderma) which would preclude definitive radiation treatment
• Previous chemotherapy for this or concurrent malignancy
• Previous concomitant malignancies except for patients with non-melanoma skin cancer, contralateral non-invasive breast cancer, prostate cancer treated with curative intent or carcinoma in situ of any other site. In addition, patients with invasive cancers treated more than 3 years previously and without evidence of recurrence will be eligible
• Women who are currently pregnant or lactating

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (4)

• Chan M, Wu L, Yun Z, McKee TD, Cabanero M, Zhao Y, Kohno M, Murakami J, de Perrot M. Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma. Commun Biol. 2021 Jul 26;4(1):914. doi: 10.1038/s42003-021-02430-5.

  PMID: 34312483 DERIVED

• Cho BCJ, Donahoe L, Bradbury PA, Leighl N, Keshavjee S, Hope A, Pal P, Cabanero M, Czarnecka K, McRae K, Tsao MS, de Perrot M. Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial. Lancet Oncol. 2021 Feb;22(2):190-197. doi: 10.1016/S1470-2045(20)30606-9. Epub 2021 Jan 12.

  PMID: 33450184 DERIVED

• de Perrot M, Dong Z, Bradbury P, Patsios D, Keshavjee S, Leighl NB, Hope A, Feld R, Cho J. Impact of tumour thickness on survival after radical radiation and surgery in malignant pleural mesothelioma. Eur Respir J. 2017 Mar 15;49(3):1601428. doi: 10.1183/13993003.01428-2016. Print 2017 Mar.

  PMID: 28298401 DERIVED

• Cho BC, Feld R, Leighl N, Opitz I, Anraku M, Tsao MS, Hwang DM, Hope A, de Perrot M. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma. J Thorac Oncol. 2014 Mar;9(3):397-402. doi: 10.1097/JTO.0000000000000078.

  PMID: 24445595 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

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

Study Officials

• John Cho, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2008
• First Posted: November 25, 2008
• Study Start: October 1, 2008
• Primary Completion: September 29, 2025
• Study Completion: September 29, 2025
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

CA (1)