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Radiosurgery With or Without Whole Brain Radiation for Multiple Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03775330
Recruitment Status : Recruiting
First Posted : December 13, 2018
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Tracking Information
First Submitted Date  ICMJE March 21, 2018
First Posted Date  ICMJE December 13, 2018
Last Update Posted Date April 14, 2021
Actual Study Start Date  ICMJE October 20, 2020
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2018)
Neurocognitive function [ Time Frame: 2 months post treatment ]
Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2018)
  • Neurocognitive function - HVLT-R [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Hopkins Verbal Learning Test-Revised (HVLT-R) (Total Recall, Delayed Recall, Delayed Recognition)
  • Neurocognitive function - Trail Making Test [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Trail Making Test (TMT, Part A and Part B)
  • Neurocognitive function - Controlled Oral Word Association [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Controlled Oral Word Association (COWA)
  • Neurocognitive function - Clinical Trial Battery Composite [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Clinical Trial Battery Composite (CTB COMP) score
  • Local control of sites initially treated by SRS [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Defined by the response criteria stipulated in the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria guideline
  • Distant tumour control within the brain [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Distant brain failure is defined as the appearance of one or more new lesions on a diagnostic-quality, contrast-enhanced MRI within the brain at sites other than those initially treated by SRS
  • Overall central nervous system (CNS) response [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Response will be recorded for each individual target lesion and for overall central nervous system (CNS) response as a composite of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status defined as per RANO-BM criteria
  • Overall survival [ Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months ]
    Response recorded for survival
  • Measure of Quality of Life [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Health-Related QoL as measured by Functional Assessment of Cancer Therapy - Brain (FACT-Br) instrument
  • Incidence of Brain Salvage therapy During Follow-up [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Number/proportion of patients requiring salvage therapy and type of salvage therapy, for progressive intracranial disease during follow-up
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 Radiosurgery With or Without Whole Brain Radiation for Multiple Metastases
Official Title  ICMJE A Randomized Trial Evaluating Stereotactic Radiosurgery Alone (SRS) to Whole Brain Radiotherapy (WBRT) Plus SRS for Patients With 5 to 20 Brain Metastases
Brief Summary This clinical study is a randomized, non-blinded, single-centre trial in patients presenting with 5 to 20 brain metastases. Eligible patients will be randomized to receive either stereotactic radiosurgery (SRS) alone or SRS plus whole brain radiation (WBRT).
Detailed Description

The current standard of care for patients with limited brain metastases (1 to 4) is stereotactic radiosurgery (SRS) alone. This has evolved from the traditional standard of care in treating patients with whole brain radiation (WBRT). Studies in patients with limited (less than 5) brain metastases have shown that WBRT is harmful with respect to neurocognition and does not improve patient survival compared to SRS alone. As a result, SRS alone now is considered the standard of care treatment for patients with limited metastases. However, there is a lack of high quality prospective randomized evidence on the role of SRS in patients with 5 or more brain metastases to guide treatment.

Therefore, this study seeks to compare SRS alone versus SRS plus WBRT in patients with 5 to 20 brain metastases in a randomized, non-blinded, single-centre trial.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Metastases
Intervention  ICMJE
  • Radiation: Stereotactic Radiosurgery (SRS)

    SRS or hypofractionated stereotactic radiation delivered via the Leksell Gammknife Perfexion/Icon radiosurgery system. Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions or 24-27 Gy in 3 fractions at the discretion of the radiation oncologist

    Maximum diameter of metastasis (doses in single fraction):

    ≤ 2 cm: 15-20 Gy > 2 cm and ≤ 3 cm: 15-18 Gy > 3 cm and ≤ 4 cm: 15 Gy

    Tumour location (doses in single fraction):

    Brainstem: 15 Gy

    Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions may be used for lesions > 2 cm at the discretion of the radiation oncologist

    Note: SRS dosing reduced by 20% (for all prescriptions > 15 Gy) when patient is randomized to SRS + WBRT arm

  • Radiation: Whole brain radiation (WBRT)
    WBRT 20 Gy in 5 fractions or 30 Gy in 10 fractions at the discretion of the radiation oncologist
Study Arms  ICMJE
  • Experimental: SRS
    Stereotactic radiosurgery
    Intervention: Radiation: Stereotactic Radiosurgery (SRS)
  • Experimental: SRS plus WBRT
    Stereotactic radiosurgery plus whole brain radiation
    Interventions:
    • Radiation: Stereotactic Radiosurgery (SRS)
    • Radiation: Whole brain radiation (WBRT)
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: December 12, 2018)
125
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologic or cytologic diagnosis of non-hematopoietic malignancy (excluding germ cell malignancies and small cell carcinoma)
  • Patients with ≥ 5 but ≤ 20 measurable brain metastases seen on a diagnostic-quality contrast-enhanced MRI obtained within 30 days prior to randomization. Patients who are found to have 21-30 metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 30 brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician
  • Age ≥ 18
  • Karnofsky Performance Status (KPS) ≥ 70
  • Baseline HVLT-R above ≥ 6
  • Patients must be able to tolerate WBRT, and all brain lesions must be eligible for treatment with SRS as determined by the radiation oncologist
  • Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
  • Able to read, speak, and understand (i.e. sufficiently fluent) English in order to allow completion and meaningful analyses of the neurocognitive tests and quality of life questionnaires

Exclusion Criteria:

  • Patients with brain metastases resulting from germ cell malignancies, small cell carcinoma, or hematologic malignancies
  • Any prior radiation therapy to the brain for brain metastases such that the study interventions cannot be delivered
  • Prior surgical resection of metastatic cancer from the brain
  • Patients with evidence of leptomeningeal disease
  • Patients who have a pacemaker or other contraindications, such that gadolinium-enhanced MRI cannot be performed or treatment cannot be delivered safely
  • Patients who have received chemotherapy or immunotherapy within 1 week prior to administration of protocol radiotherapy or who are expected / planned to receive chemotherapy within one week of completing protocol radiotherapy
  • Patients with < 5 or > 20 measureable brain metastases at time of enrollment, or > 30 brain metastases at time of treatment planning
  • Patients who are pregnant (women of child-bearing age must have negative pregnancy urine test within 7 days of randomization).
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: Delareese Mackenzie 416-480-5000 ext 7362 delareese.mackenzie@sunnybrook.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03775330
Other Study ID Numbers  ICMJE BRAIN METS SRS
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 Sunnybrook Health Sciences Centre
Study Sponsor  ICMJE Sunnybrook Health Sciences Centre
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chia-Lin Tseng, M.D. Sunnybrook Health Sciences Centre
PRS Account Sunnybrook Health Sciences Centre
Verification Date April 2021

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