Brain Metastases, AdultPhase 2IG-SRSNCT04343157
UCSD Image-Guided Cognitive-Sparing Radiosurgery for Intracranial Lesions
A Phase 2 study testing Cognitive Sparing Brain Stereotactic Radiosurgery (SRS) in people with Brain Metastases, Adult and Neurocognitive Function, run by Jona Hattangadi-Gluth at 1 site in United States.
Trial 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 for intracranial lesions, and analyze biomarkers of radiation response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Adult, Neurocognitive Function, Cancer
- What is being tested?
- Cognitive Sparing Brain Stereotactic Radiosurgery (SRS)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years or older
- Eligible for intracranial SRS: Limited brain metastases targets geometrically feasible for SRS (intact or resected tumor bed), meningioma, or cerebral AVM
- 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)
- Ability to answer questions and follow commands via neurocognitive testing
- Estimated life expectancy greater than 6 months
- Pathologic confirmation of extracerebral tumor site (eg, lung, breast, prostate) from either the primary site or a metastatic lesion if brain metastasis
- Willingness/Ability to undergo brain MRI scans
- Able to give informed consent
Who cannot join
- Pregnant or nursing women
- Women of childbearing potential unwilling to use adequate contraception
- Inability to complete a magnetic resonance imaging scan with contrast
- 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)
- Planned chemotherapy during SRS (on the day of SRS)
- Previous whole brain radiation therapy
- Leptomeningeal metastases (ineligible for SRS)
- Metastases from primary germ cell tumor, small cell carcinoma, or primary CNS lymphoma (ineligible for SRS)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moores Cancer Center
San Diego, California, 92037
Sheila Medina, 858-822-6575, s4medina@health.ucsd.edu
Jona Hattangadi-Gluth, MD
About this study
Official title: UCSD Image-Guided Cognitive-Sparing Radiosurgery for Intracranial Lesions: 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 for intracranial lesions, 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 patients with intracranial lesions.
Read the 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. SRS is also standard of care for benign intracranial lesions like arteriovenous malformations (AVMs) and meningioma.
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.
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 an anticipated 80-90 adult patients with intracranial lesions (benign tumors like meningiomas and AVMs) and limited 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.
- Conditions
- Brain Metastases, Adult, Neurocognitive Function, Cancer, Meningioma of Brain, Arteriovenous Malformations, Cerebral
- Being tested
- Cognitive Sparing Brain Stereotactic Radiosurgery (SRS)
- Medical subject headings
- Brain Neoplasms, Neoplasms, Meningioma, Intracranial Arteriovenous Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Sparing Brain Stereotactic Radiosurgery (SRS)Radiation
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 during SRS for intracranial lesions
| Study group | Role | What they receive |
|---|---|---|
| Image-guided cognitive sparing brain SRS | Experimental | 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) Receives: Radiation: Cognitive Sparing Brain Stereotactic Radiosurgery (SRS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Verbal Memory from baseline to 3 months after SRS
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.
Measured: Change from Baseline (pre-treatment) to 3 months post treatment
Change in Executive Functioning from baseline to 3 months after SRS
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
Measured: Change from Baseline (pre-treatment) to 3 months post treatment
Change in Attention/Processing Speed from baseline to 3 months after SRS
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
Measured: Change from Baseline (pre-treatment) to 3 months post treatment
Change in Language functioning from baseline to 3 months after SRS
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.
Measured: Change from Baseline (pre-treatment) to 3 months post treatment
Secondary outcomes (3)
Longitudinal changes in imaging biomarker fractional anisotropy (FA) from DTI imaging
To measure longitudinal changes in FA (unitless index between 0 and 1) from DTI imaging
Measured: baseline (pre-treatment), 3 months and 6 months post-treatment
Longitudinal changes in imaging biomarker mean diffusivity (MD) from DTI imaging
To measure longitudinal changes in MD (mm squared/second) from DTI imaging
Measured: baseline (pre-treatment), 3 months and 6 months post-treatment
Longitudinal changes in imaging biomarker volume from volumetric MR imaging
To measure longitudinal changes in volume (cc) from volumetric MR imaging
Measured: baseline (pre-treatment), 3 months and 6 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2020
- Study start1 May 2019
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for Brain Metastases, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jona Hattangadi-Gluth
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Jona Hattangadi-Gluth, University of California, San Diego
- Investigators
- Jona Hattangadi-Gluth, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04343157
- Sponsor's protocol ID
- 170848
- Other IDs
- R01CA238783-01
- Acronym
- IG-SRS
- Status last verified
- Sep 2026
- First submitted
- 2 Aug 2019
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arvold ND, Lee EQ, Mehta MP, Margolin K, Alexander BM, Lin NU, Anders CK, Soffietti R, Camidge DR, Vogelbaum MA, Dunn IF, Wen PY. Updates in the management of brain metastases. Neuro Oncol. 2016 Aug;18(8):1043-65. doi: 10.1093/neuonc/now127.
PubMed 27382120Nabors LB, Portnow J, Ammirati M, Baehring J, Brem H, Butowski N, Fenstermaker RA, Forsyth P, Hattangadi-Gluth J, Holdhoff M, Howard S, Junck L, Kaley T, Kumthekar P, Loeffler JS, Moots PL, Mrugala MM, Nagpal S, Pandey M, Parney I, Peters K, Puduvalli VK, Ragsdale J, Rockhill J, Rogers L, Rusthoven C, Shonka N, Shrieve DC, Sills AK, Swinnen LJ, Tsien C, Weiss S, Wen PY, Willmarth N, Bergman MA, Engh A. NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017. J Natl Compr Canc Netw. 2017 Nov;15(11):1331-1345. doi: 10.6004/jnccn.2017.0166.
PubMed 29118226Scoccianti S, Detti B, Cipressi S, Iannalfi A, Franzese C, Biti G. Changes in neurocognitive functioning and quality of life in adult patients with brain tumors treated with radiotherapy. J Neurooncol. 2012 Jun;108(2):291-308. doi: 10.1007/s11060-012-0821-8. Epub 2012 Feb 18.
PubMed 22354791Greene-Schloesser D, Robbins ME. Radiation-induced cognitive impairment--from bench to bedside. Neuro Oncol. 2012 Sep;14 Suppl 4(Suppl 4):iv37-44. doi: 10.1093/neuonc/nos196.
PubMed 23095829Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.
PubMed 27458945Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.
PubMed 19801201Lin NU, Wefel JS, Lee EQ, Schiff D, van den Bent MJ, Soffietti R, Suh JH, Vogelbaum MA, Mehta MP, Dancey J, Linskey ME, Camidge DR, Aoyama H, Brown PD, Chang SM, Kalkanis SN, Barani IJ, Baumert BG, Gaspar LE, Hodi FS, Macdonald DR, Wen PY; Response Assessment in Neuro-Oncology (RANO) group. Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurological, and quality-of-life outcomes. A report from the RANO group. Lancet Oncol. 2013 Sep;14(10):e407-16. doi: 10.1016/S1470-2045(13)70308-5.
PubMed 23993385Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1049-1060. doi: 10.1016/S1470-2045(17)30441-2. Epub 2017 Jul 4.
PubMed 28687377Bagadia A, Purandare H, Misra BK, Gupta S. Application of magnetic resonance tractography in the perioperative planning of patients with eloquent region intra-axial brain lesions. J Clin Neurosci. 2011 May;18(5):633-9. doi: 10.1016/j.jocn.2010.08.026. Epub 2011 Mar 2.
PubMed 21371893Abhinav K, Yeh FC, Mansouri A, Zadeh G, Fernandez-Miranda JC. High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery. Neuro Oncol. 2015 Sep;17(9):1199-209. doi: 10.1093/neuonc/nov113. Epub 2015 Jun 27.
PubMed 26117712Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci. 2008;34(1):51-61. doi: 10.1007/s12031-007-0029-0.
PubMed 18157658McDonald CR, Hagler DJ Jr, Girard HM, Pung C, Ahmadi ME, Holland D, Patel RH, Barba D, Tecoma ES, Iragui VJ, Halgren E, Dale AM. Changes in fiber tract integrity and visual fields after anterior temporal lobectomy. Neurology. 2010 Nov 2;75(18):1631-8. doi: 10.1212/WNL.0b013e3181fb44db. Epub 2010 Sep 29.
PubMed 20881271Cabezas M, Oliver A, Llado X, Freixenet J, Cuadra MB. A review of atlas-based segmentation for magnetic resonance brain images. Comput Methods Programs Biomed. 2011 Dec;104(3):e158-77. doi: 10.1016/j.cmpb.2011.07.015. Epub 2011 Aug 25.
PubMed 21871688Seibert TM, Karunamuni R, Bartsch H, Kaifi S, Krishnan AP, Dalia Y, Burkeen J, Murzin V, Moiseenko V, Kuperman J, White NS, Brewer JB, Farid N, McDonald CR, Hattangadi-Gluth JA. Radiation Dose-Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging. Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):263-269. doi: 10.1016/j.ijrobp.2016.10.035. Epub 2016 Oct 31.
PubMed 28068234Connor M, Karunamuni R, McDonald C, White N, Pettersson N, Moiseenko V, Seibert T, Marshall D, Cervino L, Bartsch H, Kuperman J, Murzin V, Krishnan A, Farid N, Dale A, Hattangadi-Gluth J. Dose-dependent white matter damage after brain radiotherapy. Radiother Oncol. 2016 Nov;121(2):209-216. doi: 10.1016/j.radonc.2016.10.003. Epub 2016 Oct 21.
PubMed 27776747
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- UCSD Image-Guided Cognitive-Sparing Radiosurgery for Intracranial Lesions: Avoidance of Eloquent White Matter and Hippocampal Regions
- ClinicalTrials.gov ID
- NCT04343157
- Acronym / sponsor ID
- IG-SRS / 170848
- Conditions
- Brain Metastases, Adult, Neurocognitive Function, Cancer, Meningioma of Brain, Arteriovenous Malformations, Cerebral
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Jona Hattangadi-GluthUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 1 May 2019 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 13 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 for intracranial lesions, 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 patients with intracranial lesions.
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. SRS is also standard of care for benign intracranial lesions like arteriovenous malformations (AVMs) and meningioma.
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.
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 an anticipated 80-90 adult patients with intracranial lesions (benign tumors like meningiomas and AVMs) and limited 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Image-guided cognitive sparing brain SRS | Experimental | Radiation: Cognitive Sparing Brain Stereotactic Radiosurgery (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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients 18 years or older
- Eligible for intracranial SRS: Limited brain metastases targets geometrically feasible for SRS (intact or resected tumor bed), meningioma, or cerebral AVM
- 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)
- Ability to answer questions and follow commands via neurocognitive testing
- Estimated life expectancy greater than 6 months
Key exclusion criteria (8 listed)
- Pregnant or nursing women
- Women of childbearing potential unwilling to use adequate contraception
- Inability to complete a magnetic resonance imaging scan with contrast
- 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)
- Planned chemotherapy during SRS (on the day of SRS)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 during SRS for intracranial lesions | Radiation | Image-guided cognitive sparing brain SRS |
Primary outcome
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 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 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 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.
3 secondary outcomes
Longitudinal changes in imaging biomarker fractional anisotropy (FA) from DTI imaging
Time frame: 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
Longitudinal changes in imaging biomarker volume from volumetric MR imaging
Time frame: baseline (pre-treatment), 3 months and 6 months post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Background: PubMed 27382120Arvold ND, Lee EQ, Mehta MP, Margolin K, Alexander BM, Lin NU, Anders CK, Soffietti R, Camidge DR, Vogelbaum MA, Dunn IF, Wen PY. Updates in the management of brain metastases. Neuro Oncol. 2016 Aug;18(8):1043-65. doi: 10.1093/neuonc/now127.
- Background: PubMed 29118226Nabors LB, Portnow J, Ammirati M, Baehring J, Brem H, Butowski N, Fenstermaker RA, Forsyth P, Hattangadi-Gluth J, Holdhoff M, Howard S, Junck L, Kaley T, Kumthekar P, Loeffler JS, Moots PL, Mrugala MM, Nagpal S, Pandey M, Parney I, Peters K, Puduvalli VK, Ragsdale J, Rockhill J, Rogers L, Rusthoven C, Shonka N, Shrieve DC, Sills AK, Swinnen LJ, Tsien C, Weiss S, Wen PY, Willmarth N, Bergman MA, Engh A. NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017. J Natl Compr Canc Netw. 2017 Nov;15(11):1331-1345. doi: 10.6004/jnccn.2017.0166.
- Background: PubMed 22354791Scoccianti S, Detti B, Cipressi S, Iannalfi A, Franzese C, Biti G. Changes in neurocognitive functioning and quality of life in adult patients with brain tumors treated with radiotherapy. J Neurooncol. 2012 Jun;108(2):291-308. doi: 10.1007/s11060-012-0821-8. Epub 2012 Feb 18.
- Background: PubMed 23095829Greene-Schloesser D, Robbins ME. Radiation-induced cognitive impairment--from bench to bedside. Neuro Oncol. 2012 Sep;14 Suppl 4(Suppl 4):iv37-44. doi: 10.1093/neuonc/nos196.
- Background: PubMed 27458945Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.
- Background: PubMed 19801201Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.
- Background: PubMed 23993385Lin NU, Wefel JS, Lee EQ, Schiff D, van den Bent MJ, Soffietti R, Suh JH, Vogelbaum MA, Mehta MP, Dancey J, Linskey ME, Camidge DR, Aoyama H, Brown PD, Chang SM, Kalkanis SN, Barani IJ, Baumert BG, Gaspar LE, Hodi FS, Macdonald DR, Wen PY; Response Assessment in Neuro-Oncology (RANO) group. Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurological, and quality-of-life outcomes. A report from the RANO group. Lancet Oncol. 2013 Sep;14(10):e407-16. doi: 10.1016/S1470-2045(13)70308-5.
- Background: PubMed 28687377Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1049-1060. doi: 10.1016/S1470-2045(17)30441-2. Epub 2017 Jul 4.
- Background: PubMed 21371893Bagadia A, Purandare H, Misra BK, Gupta S. Application of magnetic resonance tractography in the perioperative planning of patients with eloquent region intra-axial brain lesions. J Clin Neurosci. 2011 May;18(5):633-9. doi: 10.1016/j.jocn.2010.08.026. Epub 2011 Mar 2.
- Background: PubMed 26117712Abhinav K, Yeh FC, Mansouri A, Zadeh G, Fernandez-Miranda JC. High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery. Neuro Oncol. 2015 Sep;17(9):1199-209. doi: 10.1093/neuonc/nov113. Epub 2015 Jun 27.
- Background: PubMed 18157658Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci. 2008;34(1):51-61. doi: 10.1007/s12031-007-0029-0.
- Background: PubMed 20881271McDonald CR, Hagler DJ Jr, Girard HM, Pung C, Ahmadi ME, Holland D, Patel RH, Barba D, Tecoma ES, Iragui VJ, Halgren E, Dale AM. Changes in fiber tract integrity and visual fields after anterior temporal lobectomy. Neurology. 2010 Nov 2;75(18):1631-8. doi: 10.1212/WNL.0b013e3181fb44db. Epub 2010 Sep 29.
- A Phase II Randomized Trial of Proton vs. Photon Therapy (IMRT) for Cognitive Preservation in Patients with IDH Mutant, Low to Intermediate Grade Gliomas.Link provided by the sponsor.
- A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jona Hattangadi-Gluth, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cognitive Sparing Brain Stereotactic Radiosurgery (SRS) in people with Brain Metastases, Adult and Neurocognitive Function, run by Jona Hattangadi-Gluth at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sheila Medina (858-822-6575, s4medina@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Verbal Memory from baseline to 3 months after SRS (time frame: Change from Baseline (pre-treatment) to 3 months post treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04343157, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.