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

May 17, 2022 updated by: Jona Hattangadi-Gluth

UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92037
        • Recruiting
        • Moores Cancer Center
        • Contact:
        • Principal Investigator:
          • Jona Hattangadi-Gluth, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Change from Baseline (pre-treatment) to 3 months post treatment
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
Change from Baseline (pre-treatment) to 3 months post treatment
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
Change from Baseline (pre-treatment) to 3 months post treatment
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.
Change from Baseline (pre-treatment) to 3 months post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
baseline (pre-treatment), 3 months and 6 months post-treatment
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
baseline (pre-treatment), 3 months and 6 months post-treatment
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
baseline (pre-treatment), 3 months and 6 months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jona Hattangadi-Gluth

Collaborators

National Cancer Institute (NCI)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Jona Hattangadi-Gluth, MD, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

August 2, 2019

First Submitted That Met QC Criteria

April 8, 2020

First Posted (Actual)

April 13, 2020

Study Record Updates

Last Update Posted (Actual)

May 19, 2022

Last Update Submitted That Met QC Criteria

May 17, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 170848
  • R01CA238783-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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