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UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases (IG-SRS)

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ClinicalTrials.gov Identifier: NCT04343157
Recruitment Status : Recruiting
First Posted : April 13, 2020
Last Update Posted : April 30, 2021
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jona Hattangadi-Gluth, University of California, San Diego

Brief Summary:
In this proposal, the investigators introduce advanced diffusion and volumetric imaging techniques along with innovative, automated image parcellation methods to identify critical brain regions, incorporate into cognitive-sparing SRS, and analyze biomarkers of radiation response. This work will advance the investigators' understanding of neurocognitive changes after brain SRS and help create interventions that preserve cognitive-function in brain metastases patients.

Condition or disease Intervention/treatment Phase
Brain Metastases, Adult Neurocognitive Function Cancer Radiation: Cognitive Sparing Brain Stereotactic Radiosurgery (SRS) Phase 2

Detailed Description:

Background: Brain metastases affect one third of adult cancer patients. Stereotactic radiosurgery (SRS) is standard of care for patients with limited brain metastases. Yet most patients will experience post-treatment cognitive decline given the potential for high doses to eloquent white matter and the hippocampus.

Objective/Hypothesis: The investigator's team has developed innovative, robust imaging methods and automated segmentation techniques to identify critical white-matter tracts and the hippocampus using advanced diffusion tensor imaging (DTI) and volumetric imaging. These novel imaging techniques also allow us to directly and non-invasively measure microstructural changes after RT to critical brain structures in vivo. The investigators will use these advanced imaging technologies in a prospective trial of cognitive-sparing brain SRS for brain metastases patients.

Specific Aims: 1: To evaluate whether relative sparing of eloquent white matter tracts (critical for memory, language, attention, and executive functioning) and hippocampi from high doses during brain SRS results in improved 3-month post-SRS cognitive performance relative to historical controls in patients with 1 to 3 brain metastases. 2: To measure longitudinal trends in white matter damage (using DTI) and hippocampal atrophy (using volumetric change) among patients receiving cognitive-sparing brain SRS and correlate these imaging biomarkers with domain-specific cognitive outcomes.

Study Design: The investigators will prospectively enroll 60 adult patients with 1-3 brain metastases who are eligible for brain SRS and MRI. Patients will undergo MRI with DTI and 3D volumetric imaging at baseline (pre-SRS) and 1 month, 3 months, and 6 months afterwards. White matter and hippocampal segmentation will be performed and critical regions integrated into cognitive-sparing brain SRS planning with automated knowledge-based optimization. Cognitive-sparing dose constraints are derived from previous data. A well-established, validated battery of neurocognitive tests will be performed at baseline and 3 months post-SRS. Cognitive deterioration rate will be compared between the current trial and historical controls and linear regression used to analyze patient, tumor, and treatment related predictors of cognitive decline. Statistical modeling will be used to analyze changes in imaging biomarkers as a function of time and radiation dose, and these changes will be tested for association with domain-specific cognitive tests. Spatial sensitivity to RT dose across white matter tracts will be analyzed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Study patients will undergo MR imaging with DTI and 3D volumetric imaging at baseline (pre-SRS), and 1 month, 3 months, and 6 months afterwards. This regimen of post-SRS MR imaging is clinical standard of care. Segmentation of critical white matter and hippocampal volumes will be performed pre-SRS for use in brain SRS planning. Formal neurocognitive assessments will be performed at baseline and 3 months post-SRS.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Arm Intervention/treatment
Experimental: Image-guided cognitive sparing brain SRS
This is a single arm phase II study where enrolled subjects will receive intracranial SRS will performed identically to standard of care, except for implementing additional imaging techniques and software for additional regional avoidance for cognitive sparing (specifically sparing white matter and the bilateral hippocampus)
Radiation: Cognitive Sparing Brain Stereotactic Radiosurgery (SRS)
In this proposal, the investigators introduce advanced diffusion and volumetric imaging techniques along with innovative, automated image parcellation methods to identify critical brain regions, incorporate into cognitive-sparing SRS, and analyze biomarkers of radiation response. This work will advance the investigators' understanding of neurocognitive changes after brain SRS and help create interventions that preserve cognitive-function in brain metastases patients.




Primary Outcome Measures :
  1. Change in Verbal Memory from baseline to 3 months after SRS [ Time Frame: Change from Baseline (pre-treatment) to 3 months post treatment ]
    To evaluate the change from baseline to 3-month post-SRS verbal memory performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. Verbal memory outcomes and measurements include: Hopkins Verbal Learning Test-Revised (HVLT-R)-Immediate, Delayed Recall. Scale of scores is 0-36 for Immediate, 0-12 for Delayed. For both tests, higher scores indicate better performance.

  2. Change in Executive Functioning from baseline to 3 months after SRS [ Time Frame: Change from Baseline (pre-treatment) to 3 months post treatment ]

    To evaluate the change from baseline to 3-month post-SRS executive functioning performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. Executive functioning outcomes and measurements include: Controlled Oral Word Association Test (COWA): letter fluency, Trail Making Test Part B (TMT-B).

    Scale of scores is:

    Controlled Oral Word Association Test (COWA): letter fluency: 0- no upper limit. Higher score indicates better performance Trail Making Test Part B (TMT-B): 0-240. Higher score indicates poorer performance


  3. Change in Attention/Processing Speed from baseline to 3 months after SRS [ Time Frame: Change from Baseline (pre-treatment) to 3 months post treatment ]

    To evaluate the change from baseline to 3-month post-SRS Attention/Processing Speed performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. Attention/Processing Speed outcomes and measurements include: Trail Making Test Part A (TMT-A)

    Scale of scores is:

    Trail Making Test Part A (TMT-A): 0-240. Higher score indicates poorer performance


  4. Change in Language functioning from baseline to 3 months after SRS [ Time Frame: Change from Baseline (pre-treatment) to 3 months post treatment ]

    To evaluate the change from baseline to 3-month post-SRS Language performance when performing relative sparing of eloquent white matter tracts and hippocampi from high doses during brain SRS in patients with 1 to 3 brain metastases. Language outcomes and measurements include: Boston Naming Test (BNT), Controlled Oral Word Association Test (COWA): category fluency

    Scale of scores is:

    Boston Naming Test (BNT): 0-60 Controlled Oral Word Association Test (COWA): category fluency: 0-no upper limit For both tests, higher score indicates better performance.



Secondary Outcome Measures :
  1. Longitudinal changes in imaging biomarker fractional anisotropy (FA) from DTI imaging [ Time Frame: baseline (pre-treatment), 3 months and 6 months post-treatment ]
    To measure longitudinal changes in FA (unitless index between 0 and 1) from DTI imaging

  2. Longitudinal changes in imaging biomarker mean diffusivity (MD) from DTI imaging [ Time Frame: baseline (pre-treatment), 3 months and 6 months post-treatment ]
    To measure longitudinal changes in MD (mm squared/second) from DTI imaging

  3. Longitudinal changes in imaging biomarker volume from volumetric MR imaging [ Time Frame: baseline (pre-treatment), 3 months and 6 months post-treatment ]
    To measure longitudinal changes in volume (cc) from volumetric MR imaging



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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:

  1. Patients 18 years or older
  2. One to three brain metastases targets, all smaller than 3 cm in diameter (intact or resected tumor bed)
  3. Eastern cooperative Oncology Group (ECOG) performance status 0-2 (score of 0, no symptoms; 1, mild symptoms; 2, symptomatic, <50% in bed during the day)
  4. Ability to answer questions and follow commands via neurocognitive testing
  5. Estimated life expectancy greater than 6 months
  6. Pathologic confirmation of extracerebral tumor site (eg, lung, breast, prostate) from either the primary site or a metastatic lesion
  7. Willingness/Ability to undergo brain MRI scans
  8. Able to give informed consent

Exclusion Criteria:

  1. Pregnant or nursing women
  2. Women of childbearing potential unwilling to use adequate contraception
  3. Inability to complete a magnetic resonance imaging scan with contrast
  4. Tumor directly invading the critical area to be spared (for example a patient with tumor invading a critical white matter tract; ineligible for cognitive-sparing)
  5. Planned chemotherapy during SRS (on the day of SRS)
  6. Previous whole brain radiation therapy
  7. Leptomeningeal metastases (ineligible for SRS)
  8. Metastases from primary germ cell tumor, small cell carcinoma, or primary CNS lymphoma (ineligible for SRS)

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): NCT04343157


Contacts
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Contact: Lara J Rose 858-822-6575 ljrose@ucsd.edu

Locations
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United States, California
Moores Cancer Center Recruiting
San Diego, California, United States, 92037
Contact: Lara J Rose    858-822-6575    ljrose@ucsd.edu   
Principal Investigator: Jona Hattangadi-Gluth, MD         
Sponsors and Collaborators
Jona Hattangadi-Gluth
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jona Hattangadi-Gluth, MD University of California, San Diego
  Study Documents (Full-Text)

Documents provided by Jona Hattangadi-Gluth, University of California, San Diego:
Study Protocol  [PDF] July 8, 2019

Additional Information:
Publications:

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Responsible Party: Jona Hattangadi-Gluth, Associate Clinical Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04343157    
Other Study ID Numbers: 170848
R01CA238783-01 ( U.S. NIH Grant/Contract )
First Posted: April 13, 2020    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
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