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Radiosurgery With or Without Whole Brain Radiation for Multiple Metastases

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ClinicalTrials.gov Identifier: NCT03775330
Recruitment Status : Not yet recruiting
First Posted : December 13, 2018
Last Update Posted : December 13, 2018
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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).

Condition or disease Intervention/treatment Phase
Brain Metastases Radiation: Stereotactic Radiosurgery (SRS) Radiation: Whole brain radiation (WBRT) Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Trial Evaluating Stereotactic Radiosurgery Alone (SRS) to Whole Brain Radiotherapy (WBRT) Plus SRS for Patients With 5 to 20 Brain Metastases
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: SRS
Stereotactic radiosurgery
Radiation: Stereotactic Radiosurgery (SRS)

SRS or hypofractionated stereotactic radiation delivered via the Leksell Gammknife Perfexion/Icon radiosurgery system

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


Experimental: SRS plus WBRT
Stereotactic radiosurgery plus whole brain radiation
Radiation: Stereotactic Radiosurgery (SRS)

SRS or hypofractionated stereotactic radiation delivered via the Leksell Gammknife Perfexion/Icon radiosurgery system

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




Primary Outcome Measures :
  1. Neurocognitive function [ Time Frame: 2 months post treatment ]
    Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. Neurocognitive function - Controlled Oral Word Association [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Controlled Oral Word Association (COWA)

  4. Neurocognitive function - Clinical Trial Battery Composite [ Time Frame: 2 months, 4 months, 6 months, and 9 months ]
    Clinical Trial Battery Composite (CTB COMP) score

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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



Information from the National Library of Medicine

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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:

  • 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

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): NCT03775330


Contacts
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Contact: Hyla Okorofsky, RN 416-480-5000 ext 7362 hyla.okorofsky@sunnybrook.ca

Locations
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Canada, Ontario
Sunnybrook Odette Cancer Centre Not yet recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Hyla Okorofsky, RN    416-480-5000 ext 7362    hyla.okorofsky@sunnybrook.ca   
Principal Investigator: Chia-Lin (Eric) Tseng, MD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
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Principal Investigator: Chia-Lin Tseng, M.D. Sunnybrook Health Sciences Centre

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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03775330     History of Changes
Other Study ID Numbers: BRAIN METS SRS
First Posted: December 13, 2018    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018
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

Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases