Short Neoadjuvant Hemithoracic IMRT for MPM

March 12, 2024 updated by: University Health Network, Toronto

A Feasibility Study Evaluating Neoadjuvant Hemithoracic Intensity Modulated Radiation Therapy for Surgically Resectable Malignant Pleural Mesothelioma

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All
This is a single arm study. All patients enrolled will be in this arm.
Other: Pre-op RT +/- chemotherapy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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 Measures

Outcome Measure
Time Frame
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: John Cho, MD, University Health Network, Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2008

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

November 21, 2008

First Submitted That Met QC Criteria

November 24, 2008

First Posted (Estimated)

November 25, 2008

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UHN REB 08-0106-C

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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