Brain MetastasesNCT03223922
Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases
A study testing whole brain radiation therapy in people with Brain Metastases, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Brain Metastases
- What is being tested?
- whole brain radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Jul 2017to Dec 2030
- Phase
- Interventional
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic proof or unequivocal cytologic proof solid tumor malignancy. This may be obtained from either the primary or any metastatic site
- Mini Mental State Examination (MMSE) ≥24
- Age≥ 18 years
- Karnofsky Performance Status (KPS) ≥70
- Patient does not have metastases to the genu
- Patient must be scheduled to undergo treatment with whole brain radiation therapy (WBRT) to manage the brain metastases
Show all 11Show fewer
- Patients of childbearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation therapy on an unborn child
- Patient must have the ability to understand and the willingness to sign a written informed consent document
- All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines
- Patient must have a minimal life expectancy of at least 6 months
- Patients receiving prior stereostatic radiosurgery (SRS) for brain metastases are eligible
Who cannot join
- Prior WBRT
- MMSE<24
- Patient has brain metastases in the genu
- Patients must not have a serious medical or psychiatric illness that would, in the opinion of the treating physician prevent informed consent or completion of protocol treatment, and/or follow-up visits.
- KPS<70
- Non-native English speakers will be excluded since patients often lose their faculty with the language they acquired second before their native language is affected in the context of cognitive decline. This could adversely affect performance on verbal cognitive tasks.
- Patients with absolute contraindication to MRI imaging are not eligible for the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The SKCCC at Johns Hopkins
Baltimore, Maryland, 21287
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
About this study
Official title: Preservation of Cognition and Neuropsychiatric Functioning With Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases: A Pilot Study
This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases.
Read the detailed description
Efforts at treating radiation-induced cognitive and neuropsychiatric declines with medications have shown only minimal preliminary cognitive benefit and do not affect quality of life (QOL). Given the structural and functional brain alterations associated with WBRT, preventing rather than treating these radiation-induced changes may produce more favorable outcomes. Innovative radiotherapy techniques can limit the dose of radiation applied to specific brain structures without compromising tumor coverage. In this light, Radiation Therapy Oncology Group (RTOG) recently published a study evaluating the hippocampal avoidance whole brain radiation therapy (WBRT) in patients with brain metastases. They suggest potential preservation of cognitive function with this approach with no perceived detriment in survival. This concept is currently undergoing investigation in a definitive randomized controlled study (NRG-CC003) in patients receiving prophylactic cranial irradiation for small cell lung cancer. However, no other studies to date have prospectively evaluated avoidance of other particularly sensitive brain regions.
One brain region that has received little attention in the radiotherapy literature is the corpus callosum. The genu of the corpus callosum contains thin, densely packed neural fibers that primarily connect the prefrontal association areas and the anterior inferior parietal regions of the brain. Damage or thinning of the genu is associated with reduced functioning on tests of executive functioning, attention, working memory, processing speed, verbal fluency and memory in a variety of healthy and patient groups including aging, cerebral small vessel disease, traumatic brain injury, multiple sclerosis , human immunodeficiency virus, mild cognitive impairment secondary to Parkinson's disease, and euthymic bipolar disorder. The limited existing data in adults receiving WBRT for brain metastases suggest that they also perceive progressive declines in motivation following treatment. Given its apparent involvement in a wide range of cognitive processes, the genu of the corpus callosum is an excellent candidate for sparing in WBRT. This relatively small area has the potential to preserve cognitive functioning across several domains if guarded from the damaging effects of radiation. In this study patients will receive the standard whole brain radiation dose of 3000 centigray (cGy) in 10 fractions, but intensity modulated radiation therapy will be utilized to limit radiation dose to the genu of the corpus callosum. Patients will undergo cognitive testing at baseline and at 4-, 6- and 12-months following completion of brain radiation to evaluate the study hypothesis.
- Conditions
- Brain Metastases
- Being tested
- whole brain radiation therapy
- Keywords
- whole brain radiation therapy, genu of corpus callosum, cognitive function
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
whole brain radiation therapyRadiation
Also called WBRT
Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction
| Study group | Role | What they receive |
|---|---|---|
| Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy | Experimental | Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction Receives: Radiation: whole brain radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of change of cognitive function
Evaluate changes in cognition from baseline to 4 months following genu-sparing whole brain radiation therapy (GS-WBRT)
Measured: 4 months
Secondary outcomes (5)
Rate of change of white matter microstructure
Evaluate change in white matter microstructure following GS-WBRT utilizing diffusion tensor imaging
Measured: 4, 6 and 12 months
Rate of change of cognition
Evaluate changes in cognition from baseline to 4, 6 and 12 months following GS-WBRT
Measured: 4, 6 and 12 months
Time to brain metastasis
Document development of brain metastases in the spared genu of the corpus callosum
Measured: 4, 6 and 12 months
Rate of change in QoL
Document changes in QOL, neuropsychiatric symptoms, and functioning in patients receiving GS-WBRT from pre-treatment to 4, 6 and 12 months following GS-WBRT
Measured: 4, 6 and 12 months
Rate of change in other frontally-mediated functions
Document the stability of other frontally-mediated cognitive functions in those receiving GS-WBRT from pre-treatment to 4, 6 and 12 months following GS-WBRT.
Measured: 4, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start19 Jul 2017
- Primary completionDec 2026 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients will be treated to a total dose of 30 Gy with a once daily fractionation schedule of 3 Gy per fraction, administered five days per week.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristin Redmond, MD, MPH, Principal investigator, The SKCCC at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03223922
- Sponsor's protocol ID
- J1737
- Other IDs
- IRB00128471
- Status last verified
- Jun 2026
- First submitted
- 12 Jul 2017
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preservation of Cognition and Neuropsychiatric Functioning With Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases: A Pilot Study
- ClinicalTrials.gov ID
- NCT03223922
- Acronym / sponsor ID
- J1737
- Conditions
- Brain Metastases
- Keywords
- whole brain radiation therapy, genu of corpus callosum, cognitive function
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- 19 Jul 2017 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 21 Jul 2017 (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.
This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases.
Detailed description
Efforts at treating radiation-induced cognitive and neuropsychiatric declines with medications have shown only minimal preliminary cognitive benefit and do not affect quality of life (QOL). Given the structural and functional brain alterations associated with WBRT, preventing rather than treating these radiation-induced changes may produce more favorable outcomes. Innovative radiotherapy techniques can limit the dose of radiation applied to specific brain structures without compromising tumor coverage. In this light, Radiation Therapy Oncology Group (RTOG) recently published a study evaluating the hippocampal avoidance whole brain radiation therapy (WBRT) in patients with brain metastases. They suggest potential preservation of cognitive function with this approach with no perceived detriment in survival. This concept is currently undergoing investigation in a definitive randomized controlled study (NRG-CC003) in patients receiving prophylactic cranial irradiation for small cell lung cancer. However, no other studies to date have prospectively evaluated avoidance of other particularly sensitive brain regions.
One brain region that has received little attention in the radiotherapy literature is the corpus callosum. The genu of the corpus callosum contains thin, densely packed neural fibers that primarily connect the prefrontal association areas and the anterior inferior parietal regions of the brain. Damage or thinning of the genu is associated with reduced functioning on tests of executive functioning, attention, working memory, processing speed, verbal fluency and memory in a variety of healthy and patient groups including aging, cerebral small vessel disease, traumatic brain injury, multiple sclerosis , human immunodeficiency virus, mild cognitive impairment secondary to Parkinson's disease, and euthymic bipolar disorder. The limited existing data in adults receiving WBRT for brain metastases suggest that they also perceive progressive declines in motivation following treatment. Given its apparent involvement in a wide range of cognitive processes, the genu of the corpus callosum is an excellent candidate for sparing in WBRT. This relatively small area has the potential to preserve cognitive functioning across several domains if guarded from the damaging effects of radiation. In this study patients will receive the standard whole brain radiation dose of 3000 centigray (cGy) in 10 fractions, but intensity modulated radiation therapy will be utilized to limit radiation dose to the genu of the corpus callosum. Patients will undergo cognitive testing at baseline and at 4-, 6- and 12-months following completion of brain radiation to evaluate the study hypothesis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will be treated to a total dose of 30 Gy with a once daily fractionation schedule of 3 Gy per fraction, administered five days per week.
| Arm | Type | Receives |
|---|---|---|
| Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy | Experimental | Radiation: whole brain radiation therapyGenu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologic proof or unequivocal cytologic proof solid tumor malignancy. This may be obtained from either the primary or any metastatic site
- Mini Mental State Examination (MMSE) ≥24
- Age≥ 18 years
- Karnofsky Performance Status (KPS) ≥70
- Patient does not have metastases to the genu
Key exclusion criteria (7 listed)
- Prior WBRT
- MMSE<24
- Patient has brain metastases in the genu
- Patients must not have a serious medical or psychiatric illness that would, in the opinion of the treating physician prevent informed consent or completion of protocol treatment, and/or follow-up visits.
- KPS<70
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 |
|---|---|---|
| whole brain radiation therapyAlso: WBRTCorpus Callosum Genu-Sparing Whole Brain Radiation Therapy Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction | Radiation | Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy |
Primary outcome
Rate of change of cognitive function
Time frame: 4 months
Evaluate changes in cognition from baseline to 4 months following genu-sparing whole brain radiation therapy (GS-WBRT)
5 secondary outcomes
Rate of change of white matter microstructure
Time frame: 4, 6 and 12 months
Rate of change of cognition
Time frame: 4, 6 and 12 months
Time to brain metastasis
Time frame: 4, 6 and 12 months
Rate of change in QoL
Time frame: 4, 6 and 12 months
Rate of change in other frontally-mediated functions
Time frame: 4, 6 and 12 months
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 30 Jun 2026.
- 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. This study is not recruiting at the moment.
Kristin Redmond, MD, MPH principal investigator
The SKCCC at Johns Hopkins
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing whole brain radiation therapy in people with Brain Metastases, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites 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 11 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of change of cognitive function (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jun 2026.