A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection

NCT04028570 | Active Not Recruiting DMC

• 1 other identifier: 18-5987
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to find the maximum tolerated dose level for malignant pleural mesothelioma patients receiving background radiation + boost radiation, and surgery. Boost radiation is an experimental form of radiation that involves targeting non-uniform high doses of radiation to bulky pleural masses. We hypothesize the immunologic abscopal effect is an important component in controlling disease, and may be stimulated with highly hypofractionated doses. Doses will increase with every three patients who will be enrolled in the study until the background radiation reaches 1800 cGy or the maximum tolerated dose, whichever is lower.

Conditions

Mesothelioma; Lung

Keywords

Radiation; Boost Radiation Therapy; Background Radiation Therapy; Surgery; Extensive Pleural Resection

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose for Background Radiation

  AEs will be graded by CTCAE. Maximum tolerated dose is the dose level that do not result in fatal lung injury (grade 5 lung toxicity) or life-threatening or fatal treatment related toxicity (grade 4+).

  Up to five years

Secondary Outcomes (11)

• Patient Morbidity

  Up to five years

• Local recurrence

  Up to five years

• Patients' quality of life

  Up to five years

• Evaluating patients' pain

  Up to five years

• Evaluating patients' pain

  Up to five years

Study Arms (1)

Radiation

EXPERIMENTAL

This study involves a 3+3 design. The starting cohort (n=3) will receive a neoadjuvant Background dose to the affected hemithorax (starting at 0 cGy) as well as concomitant Boost dose (of at least 2100 cGy) to a part of the gross tumour volume (GTV). The radiation will be delivered over 3 alternate days over 5-7 calendar days followed by macroscopically complete extensive pleural resection (either extra-pleural pneumonectomy or extended pleurectomy decortication, at the surgeon's discretion) after 7 to 14 days. If no dose limiting toxicities (DLTs) seen, then the Background RT dose will be increased by 600 cGy (up to 1800 cGy) and the cohort (n=3) for the next dose level will be accrued. If only 1 DLT seen, then an additional 3 patients will be treated on this dose level. If 2 or more DLTs seen at any given dose level, then the previous dose level will be defined as the maximum tolerated dose (MTD). Patients will be stratified by type of resection.

Radiation: Varying Doses of Background and Boost RT

Interventions

Varying Doses of Background and Boost RT RADIATION

3+3 radiation dose escalation model to see the maximum tolerated dose for background and boost radiation therapy.

Radiation

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Good pulmonary function precluding radiation therapy (FEV1\>1 L or \>40% predicted or DLCO \>45% predicted)
• Any patient with a new histological diagnosis of malignant pleural mesothelioma (MPM). Sarcomatoid or biphasic histologies can be included but will be analyzed separately due to their poor prognosis.
• Stage T1-3 N0-1 M0 according to the 8th edition of the tumor, node, and metastases (TNM) staging system based on conventional investigations and tests (Appendix 1). Note that the updated TNM staging system now categorizes ipsilateral mediastinal nodes as N1 disease.
• Suitable for combined modality therapy
• Informed consent.

You may not qualify if:

• Age \< 18 years.
• Contralateral mediastinal nodal disease (N2)
• Distant metastatic disease (M1).
• Poor performance status ECOG 3-4.
• Poor pulmonary function precluding radiation therapy (FEV1\<1 L or \<40% predicted or diffusion lung capacity for carbon monoxide (DLCO) \<45% predicted)
• Failure to provide informed consent.
• 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 or 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)

Princess Margaret Hospital, University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Mesothelioma

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Study Officials

• John Cho, MD, PhD

  Princess Margaret Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3 radiation dose escalation

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: July 22, 2019
• Study Start: September 5, 2019
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)