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

Primary Purpose

Mesothelioma; Lung

Status
Active
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Varying Doses of Background and Boost RT
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesothelioma; Lung focused on measuring Radiation, Boost Radiation Therapy, Background Radiation Therapy, Surgery, Extensive Pleural Resection

Eligibility Criteria

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Princess Margaret Hospital, University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radiation

Arm Description

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.

Outcomes

Primary Outcome Measures

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+).

Secondary Outcome Measures

Patient Morbidity
NCI common toxicity scale
Local recurrence
Documented radiographically
Patients' quality of life
Short Form Health Survey-36 (SF-36) Form
Evaluating patients' pain
Assess by using the Short Form (BPI-SF)
Evaluating patients' pain
Assess by using The Hospital Anxiety and Depression Scale (HADS)
Evaluating patients' pain
Assess by using the EuroQol EQ-5D-5L Questionnaire
Evaluating patients' pain
Assess by using the Sensitivity to Pain Traumatization Scale (SPTS)
Evaluating patients' pain
Assess by using the ID Pain form
Evaluating patients' pain
Assess by using the Pain Catastrophizing Scale (PCS)
Evaluating patients' pain
Assess by using the Post-traumatic Stress Disorder Checklist-Civilian version (PCL-C)
Evaluating patients' pain
Assess by using a variety of standard instruments including the Injustice Experience Questionnaire (IEQ).

Full Information

First Posted
April 3, 2019
Last Updated
April 5, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT04028570
Brief Title
A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection
Acronym
SMARTER
Official Title
A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 5, 2019 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2025 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This study aims to find the maximum tolerated dose level for mesothelioma patients receiving background radiation + boost radiation, and surgery. 3 patients will start with a background radiation therapy (RT) dose of 0 cGy, and boost RT of at least 2100 cGy. If the radiation is manageable (radiation related AEs grade < 4), the next set of 3 patients will be enrolled, and the background radiation dose will be increased by 600 cGy. This will continue until the background radiation dose reaches 1800 cGy. If 1 patient exhibits dose limiting toxicities (AEs grade 4 & 5), the dose level will repeat with the next 3 patients. If 2 or more patients exhibit DLTs, the previous dose level will be determined as the maximum tolerated dose level. Surgery will be scheduled to occur approximately 1-2 weeks after completing radiation therapy, and will subsequently be followed up as per study schedule.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma; Lung
Keywords
Radiation, Boost Radiation Therapy, Background Radiation Therapy, Surgery, Extensive Pleural Resection

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
3+3 radiation dose escalation
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Radiation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Varying Doses of Background and Boost RT
Intervention Description
3+3 radiation dose escalation model to see the maximum tolerated dose for background and boost radiation therapy.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose for Background Radiation
Description
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+).
Time Frame
Up to five years
Secondary Outcome Measure Information:
Title
Patient Morbidity
Description
NCI common toxicity scale
Time Frame
Up to five years
Title
Local recurrence
Description
Documented radiographically
Time Frame
Up to five years
Title
Patients' quality of life
Description
Short Form Health Survey-36 (SF-36) Form
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using the Short Form (BPI-SF)
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using The Hospital Anxiety and Depression Scale (HADS)
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using the EuroQol EQ-5D-5L Questionnaire
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using the Sensitivity to Pain Traumatization Scale (SPTS)
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using the ID Pain form
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using the Pain Catastrophizing Scale (PCS)
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using the Post-traumatic Stress Disorder Checklist-Civilian version (PCL-C)
Time Frame
Up to five years
Title
Evaluating patients' pain
Description
Assess by using a variety of standard instruments including the Injustice Experience Questionnaire (IEQ).
Time Frame
Up to five years

10. Eligibility

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

12. IPD Sharing Statement

Plan to Share IPD
No

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

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