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

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ClinicalTrials.gov Identifier: NCT04028570
Recruitment Status : Recruiting
First Posted : July 22, 2019
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Mesothelioma; Lung Radiation: Varying Doses of Background and Boost RT Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 radiation dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: Radiation
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
3+3 radiation dose escalation model to see the maximum tolerated dose for background and boost radiation therapy.




Primary Outcome Measures :
  1. Maximum Tolerated Dose for Background Radiation [ Time Frame: Up to five years ]
    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 :
  1. Patient Morbidity [ Time Frame: Up to five years ]
    NCI common toxicity scale

  2. Local recurrence [ Time Frame: Up to five years ]
    Documented radiographically

  3. Patients' quality of life [ Time Frame: Up to five years ]
    Short Form Health Survey-36 (SF-36) Form

  4. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Short Form (BPI-SF)

  5. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using The Hospital Anxiety and Depression Scale (HADS)

  6. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the EuroQol EQ-5D-5L Questionnaire

  7. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Sensitivity to Pain Traumatization Scale (SPTS)

  8. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the ID Pain form

  9. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Pain Catastrophizing Scale (PCS)

  10. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Post-traumatic Stress Disorder Checklist-Civilian version (PCL-C)

  11. Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using a variety of standard instruments including the Injustice Experience Questionnaire (IEQ).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028570


Contacts
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Contact: John Cho, MD, PhD 416-946-4501 ext 6513 John.Cho@rmp.uhn.ca

Locations
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Canada, Ontario
Princess Margaret Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: John Cho, MD    416-946-4501 ext 2124    john.cho@rmp.uhn.on.ca   
Principal Investigator: John Cho, MD         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: John Cho, MD, PhD Princess Margaret Hospital, Canada

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04028570    
Other Study ID Numbers: 18-5987
First Posted: July 22, 2019    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
Radiation
Boost Radiation Therapy
Background Radiation Therapy
Surgery
Extensive Pleural Resection
Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial