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UNITy-BasED MR-Linac Adaptive Simultaneous Integrated Hypofractionationed Boost Trial for High Grade Glioma in the Elderly (UNITED2)

Primary Purpose

Glioblastoma Multiforme, Adult, Glioblastoma, IDH-mutant

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Dose escalation + Reduced Margin Adaptive Radiotherapy
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme, Adult

Eligibility Criteria

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

Inclusion Criteria:

  • Patient age ≥ 65 years
  • Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma or WHO grade 4 astrocytoma, IDH-mutant
  • Biopsy or surgical resection performed ≤ 6 weeks prior to study entry
  • Deemed suitable by the treating physicians for 15 daily fractions of radiation, delivered daily over 3 weeks, with concurrent temozolomide chemotherapy
  • Expected survival ≥ 12 weeks
  • ECOG performance status of 0, 1 or 2
  • Able (sufficiently fluent in English) and willing to complete QOL questionnaires; however, inability to complete the questionnaires will not make the patient ineligible for the study
  • Sufficient estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 to allow administration of gadolinium-based contrast agent; patients with eGFR < 30 mL/min/1.73 m2 not on dialysis may be allowed on the study after discussion of risks and benefits and approval by study neuroradiologist(s)
  • Completed written informed consent
  • Patient must be accessible for treatment and follow-up

Exclusion Criteria:

  • Contraindications to MRI as per standard MRI screening policy
  • Contraindication to Gadolinium-based contrast media
  • Inability to lie flat in a supine position for at least 90 minutes
  • Inability to tolerate immobilization in a head thermoplastic mask
  • Patients > 140 kg and/or a circumference > 60 cm
  • Prior dose-limiting cranial irradiation
  • T1w post-gadolinium enhancing disease involving the brainstem
  • Leptomeningeal dissemination of disease
  • Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment Arm

    Arm Description

    Concurrent dose-escalated chemoradiation with temozolomide (TMZ) on the MR-Linac with weekly adaptation

    Outcomes

    Primary Outcome Measures

    Progression-free survival at 6 months following chemoradiation

    Secondary Outcome Measures

    Overall survival
    The time interval between study start date and date of death from any cause
    Progression-free survival
    The time interval between study start date and date of disease progression or death, whichever comes first
    Local control
    As assessed on imaging using the Response Assessment Criteria for High-Grade Gliomas (RANO-HGG)
    Patterns of Failure
    The risk of local, marginal, and distant failure at the time of progression
    Toxicity and Health-related Quality of Life Changes based on the EORTC QLQ-C30
    Adverse events and changes in quality of life before, during, and after chemoradiation therapy
    Toxicity and Health-related Quality of Life Changes based on the EORTC QLQ-BN20
    Adverse events and changes in quality of life before, during, and after chemoradiation therapy
    Compare differences in adaptive vs non-adaptive with regards to treatment volume
    Differences in treatment volume using adaptive vs. non-adaptive treatment planning will be compared
    Compare differences in adaptive vs non-adaptive with regards to organ-at-risk doses
    Differences in dosing to organs-at-risk using adaptive vs. non-adaptive treatment planning will be compared
    Compare differences in adaptive vs non-adaptive with regards to cumulative dose
    Differences in cumulative dose of radiation using adaptive vs. non-adaptive treatment planning will be compared
    Compare differences in adaptive vs non-adaptive with regards to length of radiation treatment time
    Differences in time for radiation treatment using adaptive vs. non-adaptive treatment planning will be compared
    Functional Imaging Kinetics as a Correlate of Treatment Response
    Temporal changes of functional imaging metrics will be correlated with clinical outcomes

    Full Information

    First Posted
    September 23, 2022
    Last Updated
    October 3, 2022
    Sponsor
    Sunnybrook Health Sciences Centre
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05565521
    Brief Title
    UNITy-BasED MR-Linac Adaptive Simultaneous Integrated Hypofractionationed Boost Trial for High Grade Glioma in the Elderly
    Acronym
    UNITED2
    Official Title
    UNITy-BasED MR-Linac Adaptive Simultaneous Integrated Hypofractionationed Boost Trial for High Grade Glioma in the Elderly
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 15, 2022 (Anticipated)
    Primary Completion Date
    December 31, 2024 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sunnybrook Health Sciences Centre

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The usual standard of care for patients over 65 diagnosed with glioblastoma ("GBM") or Grade 4 astrocytoma, IDH-mutant is a 3-week course of radiotherapy, with concurrent and adjuvant temozolomide (TMZ). This radiation dose and length of treatment are less than what would be given for younger patients, primarily due to unclear survival benefits from randomized trials. However, survival remains dismal, and may be partially due to the reduced radiation dose. Recent studies investigating this have found that increased radiation dose (to the equivalent of what is normally given over 6 weeks in younger patients) over 3 weeks is well-tolerated and has improved survival rates. Additionally, with the advent of novel technology such as the MR-Linac, adaptive radiotherapy with this regimen using reduced radiation margins is possible. Use of the MR-Linac allows for daily MRI scans to be done prior to treatment, so plans can be adapted to tumour dynamics and anatomical deformations. In this trial, we will examine the outcomes of increased radiation dose, combined with reduced-margin adaptive radiotherapy in this patient population.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Glioblastoma Multiforme, Adult, Glioblastoma, IDH-mutant

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    55 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment Arm
    Arm Type
    Experimental
    Arm Description
    Concurrent dose-escalated chemoradiation with temozolomide (TMZ) on the MR-Linac with weekly adaptation
    Intervention Type
    Radiation
    Intervention Name(s)
    Dose escalation + Reduced Margin Adaptive Radiotherapy
    Intervention Description
    Concurrent chemoradiation with temozolomide (TMZ) over 3 weeks (40Gy in 15 fractions). The gross tumor volume (GTV) plus margin will be boosted simultaneously (SIB) to 52.5 Gy in 15 fractions. Radiation will be delivered on the MR-Linac with a reduced clinical target volume (CTV) margin of 5 mm and a weekly online adaptive approach.
    Primary Outcome Measure Information:
    Title
    Progression-free survival at 6 months following chemoradiation
    Time Frame
    6 months from study entry date
    Secondary Outcome Measure Information:
    Title
    Overall survival
    Description
    The time interval between study start date and date of death from any cause
    Time Frame
    Through study completion, an average of 9 months
    Title
    Progression-free survival
    Description
    The time interval between study start date and date of disease progression or death, whichever comes first
    Time Frame
    Through study completion, an average of 5 months
    Title
    Local control
    Description
    As assessed on imaging using the Response Assessment Criteria for High-Grade Gliomas (RANO-HGG)
    Time Frame
    Through study completion, an average of 5 months
    Title
    Patterns of Failure
    Description
    The risk of local, marginal, and distant failure at the time of progression
    Time Frame
    Through study completion, an average of 5 months
    Title
    Toxicity and Health-related Quality of Life Changes based on the EORTC QLQ-C30
    Description
    Adverse events and changes in quality of life before, during, and after chemoradiation therapy
    Time Frame
    Through study completion, an average of 9 months
    Title
    Toxicity and Health-related Quality of Life Changes based on the EORTC QLQ-BN20
    Description
    Adverse events and changes in quality of life before, during, and after chemoradiation therapy
    Time Frame
    Through study completion, an average of 9 months
    Title
    Compare differences in adaptive vs non-adaptive with regards to treatment volume
    Description
    Differences in treatment volume using adaptive vs. non-adaptive treatment planning will be compared
    Time Frame
    6-12 months
    Title
    Compare differences in adaptive vs non-adaptive with regards to organ-at-risk doses
    Description
    Differences in dosing to organs-at-risk using adaptive vs. non-adaptive treatment planning will be compared
    Time Frame
    6-12 months
    Title
    Compare differences in adaptive vs non-adaptive with regards to cumulative dose
    Description
    Differences in cumulative dose of radiation using adaptive vs. non-adaptive treatment planning will be compared
    Time Frame
    6-12 months
    Title
    Compare differences in adaptive vs non-adaptive with regards to length of radiation treatment time
    Description
    Differences in time for radiation treatment using adaptive vs. non-adaptive treatment planning will be compared
    Time Frame
    6-12 months
    Title
    Functional Imaging Kinetics as a Correlate of Treatment Response
    Description
    Temporal changes of functional imaging metrics will be correlated with clinical outcomes
    Time Frame
    12-24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patient age ≥ 65 years Histopathologically confirmed, based on biopsy or surgical resection, glioblastoma or WHO grade 4 astrocytoma, IDH-mutant Biopsy or surgical resection performed ≤ 6 weeks prior to study entry Deemed suitable by the treating physicians for 15 daily fractions of radiation, delivered daily over 3 weeks, with concurrent temozolomide chemotherapy Expected survival ≥ 12 weeks ECOG performance status of 0, 1 or 2 Able (sufficiently fluent in English) and willing to complete QOL questionnaires; however, inability to complete the questionnaires will not make the patient ineligible for the study Sufficient estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 to allow administration of gadolinium-based contrast agent; patients with eGFR < 30 mL/min/1.73 m2 not on dialysis may be allowed on the study after discussion of risks and benefits and approval by study neuroradiologist(s) Completed written informed consent Patient must be accessible for treatment and follow-up Exclusion Criteria: Contraindications to MRI as per standard MRI screening policy Contraindication to Gadolinium-based contrast media Inability to lie flat in a supine position for at least 90 minutes Inability to tolerate immobilization in a head thermoplastic mask Patients > 140 kg and/or a circumference > 60 cm Prior dose-limiting cranial irradiation T1w post-gadolinium enhancing disease involving the brainstem Leptomeningeal dissemination of disease Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Chia-Lin (Eric) Tseng, MD
    Phone
    416-480-6100
    Ext
    4998
    Email
    chia-lin.tseng@sunnybrook.ca

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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