4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection (SMARTER)

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

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.

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.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
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
Actual Study Start Date : September 5, 2019
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2025
Arms and Interventions
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.
Outcome Measures
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).


Eligibility Criteria
Layout table for eligibility information
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.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: John Cho, MD, PhD 416-946-4501 ext 6513 John.Cho@rmp.uhn.ca

Locations
Layout table for location information
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
Layout table for investigator information
Principal Investigator: John Cho, MD, PhD Princess Margaret Hospital, Canada
Tracking Information
First Submitted Date  ICMJE April 3, 2019
First Posted Date  ICMJE July 22, 2019
Last Update Posted Date April 13, 2021
Actual Study Start Date  ICMJE September 5, 2019
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2019) 		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+).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
  • Patient Morbidity [ Time Frame: Up to five years ]
    NCI common toxicity scale
  • Local recurrence [ Time Frame: Up to five years ]
    Documented radiographically
  • Patients' quality of life [ Time Frame: Up to five years ]
    Short Form Health Survey-36 (SF-36) Form
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Short Form (BPI-SF)
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using The Hospital Anxiety and Depression Scale (HADS)
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the EuroQol EQ-5D-5L Questionnaire
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Sensitivity to Pain Traumatization Scale (SPTS)
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the ID Pain form
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Pain Catastrophizing Scale (PCS)
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using the Post-traumatic Stress Disorder Checklist-Civilian version (PCL-C)
  • Evaluating patients' pain [ Time Frame: Up to five years ]
    Assess by using a variety of standard instruments including the Injustice Experience Questionnaire (IEQ).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection
Official Title  ICMJE A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy Using Extensive Pleural Resection
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
3+3 radiation dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mesothelioma; Lung
Intervention  ICMJE 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.
Study Arms  ICMJE 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.
Intervention: Radiation: Varying Doses of Background and Boost RT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2019) 		18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2025
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John Cho, MD, PhD 416-946-4501 ext 6513 John.Cho@rmp.uhn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04028570
Other Study ID Numbers  ICMJE 18-5987
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John Cho, MD, PhD Princess Margaret Hospital, Canada
PRS Account University Health Network, Toronto
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

治疗案例

前沿医讯