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Short Neoadjuvant Hemithoracic IMRT for MPM

Primary Purpose

Malignant Pleural Mesothelioma

Status
Active
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Pre-op RT +/- chemotherapy
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring MPM, Short hemithoracic IMRT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
November 21, 2008
Last Updated
April 5, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT00797719
Brief Title
Short Neoadjuvant Hemithoracic IMRT for MPM
Official Title
A Feasibility Study Evaluating Neoadjuvant Hemithoracic Intensity Modulated Radiation Therapy for Surgically Resectable Malignant Pleural Mesothelioma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2008 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The study is a phase I/II prospective single cohort clinical feasibility study. 100 patients with early stage resectable malignant pleural mesothelioma will be enrolled into the study. Patients will have a baseline PET scan. Patients on the study will receive IMRT for approximately 1 week of 5 daily treatments. 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 OR Pemetrexed and cisplatin, will be given 6-12 weeks post-surgery. Before and during treatment, side effects will be assessed. After treatment, follow up visits will be conducted every 1 to 2 months for the first year, and every 3 months for the second year. At each visit, a history and physical examination will be performed and ECOG performance status will be assessed. Routine tests will include CBC, liver profile, creatinine and chest x-ray. CT thorax and abdomen will be done at 3, 6, 12, 18, and 24 months. Additional test may be done at the discretion of the oncologist if the patient becomes symptomatic. The study will evaluate the feasibility and safety of short pre-operative RT, and may help confirm the intraoperative seeding hypothesis. Preoperative RT may also reduce the risk of both local and distant spread and, ultimately, improve overall survival. By shortening overall treatment time, it may also improve patient compliance and convenience. We may be able to give chemotherapy only to patients that are at highest risk and avoid it in others.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
MPM, Short hemithoracic IMRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All
Arm Type
Experimental
Arm Description
This is a single arm study. All patients enrolled will be in this arm.
Intervention Type
Other
Intervention Name(s)
Pre-op RT +/- chemotherapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
The primary outcome for the study will be the proportion of patients treated as per protocol without treatment related mortality.
Time Frame
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 Outcome Measure Information:
Title
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
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Cho, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
34312483
Citation
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.
Results Reference
derived
PubMed Identifier
33450184
Citation
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.
Results Reference
derived
PubMed Identifier
28298401
Citation
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.
Results Reference
derived
PubMed Identifier
24445595
Citation
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.
Results Reference
derived

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Short Neoadjuvant Hemithoracic IMRT for MPM

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