Brain MetastasisNCT03223675
Neurocognitive Impact and Dose-Effect Relationship of Hippocampal Avoidance During Whole Brain Radiotherapy Plus Simultaneous Integrated Boost - A Prospective Follow-up Study
A study testing hippocampal-sparing WBRT in people with Brain Metastasis and Brain Metastases, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
For newly-diagnosed patients with brain metastasis, whole brain radiation therapy (WBRT) probably remains a common palliative management even for those with oligometastatic brain disease. However, WBRT-related late sequelae, particularly a decline in neurocognitive functions (NCFs), are a major concern. Read more about this study
- Who is it for?
- Ages 20 to 84 years
- Conditions the study is for
- Brain Metastasis, Brain Metastases
- What is being tested?
- hippocampal-sparing WBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Apr 2016to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 20 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for therapeutic or prophylactic WBRT
- Good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or a general status of Karnofsky Score (KPS) at least 70 %
- The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 3 cm
Who cannot join
- Patients with MRI-identified metastasis within 5 mm perihippocampally
- Patients with metastasis involving the brain stem
- Clinical suspicion of leptomeningeal spreading
- Patients with a solitary brain metastatic lesion which had been totally removed
- History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Chang Gung Memorial Hospital
Taoyuan, 333
Shinn-Yn Lin, M.D., +886-33281200 ext. 7172, rt3126@gmail.com
About this study
For newly-diagnosed patients with brain metastasis, whole brain radiation therapy (WBRT) probably remains a common palliative management even for those with oligometastatic brain disease. However, WBRT-related late sequelae, particularly a decline in neurocognitive functions (NCFs), are a major concern. More importantly, in patients with limited brain metastases and a fair/good performance status, sparing the radiosensitive and vulnerable structures which are responsible for essential NCFs during the WBRT course is one of the reasonable strategies to postpone and prevent the development of WBRT-induced neurocognitive impairments. Actually, radiation-related neurocognitive dysfunction is usually characterized as a decline involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role. In addition to the neurocognitive preservation by virtue of sparing the radiosensitive structures like the hippocampus, durable intracranial tumor control critically depends on an escalated radiotherapeutic dose level which is adequate enough to eradicate gross metastatic brain lesions. Therefore, in order to achieve both hippocampal sparing and simultaneous integrated boost(s) to gross metastatic foci, a specialized WBRT technique, hippocampal avoidance during WBRT plus simultaneous integrated boost (SIB) will be adopted in this prospective study. Moreover, the dose-effect relationship would be analyzed in order to explore the correlation between the equivalent uniform dose (EUD) irradiating the hippocampus and the neurocognitive change/decline after the above WBRT course measured by objective neurocognitive test tools. Newly-diagnosed cancer patients harboring 1-3 gross metastatic lesions but still in fair/good performance statuses are potentially eligible. All recruited patients should receive baseline functional brain MRI examination and baseline neurobehavioral assessment. Treatment planning will be designed via the technique of volumetric-modulated arc therapy (VMAT) to achieve both hippocampal avoidance and simultaneous integrated boost(s) to gross metastatic lesions. Except for the above regions for which conformal avoidance or SIB is attempted, the prescribed dose to the remaining brain parenchyma will be consistently 3000 cGy in 12 fractions. Accordingly, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal and non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurobehavioral functions for our registered patients. The primary outcome measure is delayed recall, as determined by the change/decline in verbal memory or non-verbal memory, from the baseline assessment to 4 months after the start of the WBRT course. This prospective cohort study aims to examine thoroughly the impact of a specialized WBRT technique, integrating both simultaneous integrated boost(s) delivered to gross metastatic foci and conformal hippocampal avoidance, on the status of NCF change/decline in patients with oligometastatic brain disease. It is anticipated that intracranial local control will be more sustainable and durable resulting from the escalated focal dose of SIBs. Ultimately, we also expect the dose-effect relationship will be clearly demonstrated after investigating the correlation between the hippocampal dosimetry and the status of NCF change/decline after receiving HA-WBRT plus SIB.
- Conditions
- Brain Metastasis, Brain Metastases
- Being tested
- hippocampal-sparing WBRT
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hippocampal-sparing WBRTRadiation
| Study group | Role | What they receive |
|---|---|---|
| Hippocampus-sparing WBRT plus SIB | Experimental | All studied patients should undergo a computed tomography (CT) simulation scan encompassing the entire head region with 1.25-mm slice thickness using a thermoplastic mask for immobilization. To achieve conformal hippocampal sparing during the delivery of whole brain radiation (WBRT) and simultaneous integrated boost(s) (SIB), the technique of volumetric modulated arc therapy (VMAT) via Linac-based RapidArc®.In terms of dose prescription, a dose of 30 Gy in 12 fractions was prescribed to whole-brain planning target volume (PTV) containing the normal brain parenchyma; an simultaneous integrated boost up to 120 - 150% is attempted to irradiate the gross metastatic foci. Receives: Radiation: hippocampal-sparing WBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (WMS III- Word List score) from the baseline assessment to 4 months after the start of HS-WBRT.
Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT
Measured: 4 months after the start of HS-WBRT
The primary endpoint is delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of HS-WBRT
Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.
Measured: 4 months after the start of HS-WBRT
Secondary outcomes (2)
Overall survival time, indicated by the time from the date of recruitment to the date of expiring
Measured: up to 18 months
The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI or CT
Measured: up to 18 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 start1 Apr 2016
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasisStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03223675
- Sponsor's protocol ID
- 104-9176A3
- Status last verified
- Apr 2023
- First submitted
- 22 Jun 2017
- Last updated
- 1 May 2023
- Results posted
- No
- Individual data sharing
- No
Publications
Lin SY, Tsan DL, Chuang CC, Yang CC, Pai PC, Wang CL, Wu YM, Lee CC, Lin CH, Wei KC, Chou WC. Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan. Front Oncol. 2022 Jan 12;11:784635. doi: 10.3389/fonc.2021.784635. eCollection 2021.
PubMed 35096584
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurocognitive Impact and Dose-Effect Relationship of Hippocampal Avoidance During Whole Brain Radiotherapy Plus Simultaneous Integrated Boost - A Prospective Follow-up Study
- ClinicalTrials.gov ID
- NCT03223675
- Acronym / sponsor ID
- 104-9176A3
- Conditions
- Brain Metastasis, Brain Metastases
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (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.
For newly-diagnosed patients with brain metastasis, whole brain radiation therapy (WBRT) probably remains a common palliative management even for those with oligometastatic brain disease. However, WBRT-related late sequelae, particularly a decline in neurocognitive functions (NCFs), are a major concern. More importantly, in patients with limited brain metastases and a fair/good performance status, sparing the radiosensitive and vulnerable structures which are responsible for essential NCFs during the WBRT course is one of the reasonable strategies to postpone and prevent the development of WBRT-induced neurocognitive impairments. Actually, radiation-related neurocognitive dysfunction is usually characterized as a decline involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role. In addition to the neurocognitive preservation by virtue of sparing the radiosensitive structures like the hippocampus, durable intracranial tumor control critically depends on an escalated radiotherapeutic dose level which is adequate enough to eradicate gross metastatic brain lesions. Therefore, in order to achieve both hippocampal sparing and simultaneous integrated boost(s) to gross metastatic foci, a specialized WBRT technique, hippocampal avoidance during WBRT plus simultaneous integrated boost (SIB) will be adopted in this prospective study. Moreover, the dose-effect relationship would be analyzed in order to explore the correlation between the equivalent uniform dose (EUD) irradiating the hippocampus and the neurocognitive change/decline after the above WBRT course measured by objective neurocognitive test tools. Newly-diagnosed cancer patients harboring 1-3 gross metastatic lesions but still in fair/good performance statuses are potentially eligible. All recruited patients should receive baseline functional brain MRI examination and baseline neurobehavioral assessment. Treatment planning will be designed via the technique of volumetric-modulated arc therapy (VMAT) to achieve both hippocampal avoidance and simultaneous integrated boost(s) to gross metastatic lesions. Except for the above regions for which conformal avoidance or SIB is attempted, the prescribed dose to the remaining brain parenchyma will be consistently 3000 cGy in 12 fractions. Accordingly, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal and non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurobehavioral functions for our registered patients. The primary outcome measure is delayed recall, as determined by the change/decline in verbal memory or non-verbal memory, from the baseline assessment to 4 months after the start of the WBRT course. This prospective cohort study aims to examine thoroughly the impact of a specialized WBRT technique, integrating both simultaneous integrated boost(s) delivered to gross metastatic foci and conformal hippocampal avoidance, on the status of NCF change/decline in patients with oligometastatic brain disease. It is anticipated that intracranial local control will be more sustainable and durable resulting from the escalated focal dose of SIBs. Ultimately, we also expect the dose-effect relationship will be clearly demonstrated after investigating the correlation between the hippocampal dosimetry and the status of NCF change/decline after receiving HA-WBRT plus SIB.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hippocampus-sparing WBRT plus SIB | Experimental | Radiation: hippocampal-sparing WBRTAll studied patients should undergo a computed tomography (CT) simulation scan encompassing the entire head region with 1.25-mm slice thickness using a thermoplastic mask for immobilization. To achieve conformal hippocampal sparing during the delivery of whole brain radiation (WBRT) and simultaneous integrated boost(s) (SIB), the technique of volumetric modulated arc therapy (VMAT) via Linac-based RapidArc®.In terms of dose prescription, a dose of 30 Gy in 12 fractions was prescribed to whole-brain planning target volume (PTV) containing the normal brain parenchyma; an simultaneous integrated boost up to 120 - 150% is attempted to irradiate the gross metastatic foci. |
Who may qualify
- Ages
- 20 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for therapeutic or prophylactic WBRT
- Good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or a general status of Karnofsky Score (KPS) at least 70 %
- The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 3 cm
Key exclusion criteria (5 listed)
- Patients with MRI-identified metastasis within 5 mm perihippocampally
- Patients with metastasis involving the brain stem
- Clinical suspicion of leptomeningeal spreading
- Patients with a solitary brain metastatic lesion which had been totally removed
- History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons
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 |
|---|---|---|
| hippocampal-sparing WBRT | Radiation | Hippocampus-sparing WBRT plus SIB |
Primary outcome
The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (WMS III- Word List score) from the baseline assessment to 4 months after the start of HS-WBRT.
Time frame: 4 months after the start of HS-WBRT
Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III) - Word List score] from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT
The primary endpoint is delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of HS-WBRT
Time frame: 4 months after the start of HS-WBRT
Neurocognitive assessment: including memory, executive functions, and psychomotor speed. This neurocognitive outcome was delayed recall, as determined by the change/decline in non-verbal memory (WMS III- Visual Reproduction score) from the baseline assessment to 4 months after the start of the course of WBRT with hippocampus sparing (HS-WBRT). Additionally, the follow-up of neurocognitive assessment will also be administered at 12 months and up to 18 months after the start of HS-WBRT.
2 secondary outcomes
Overall survival time, indicated by the time from the date of recruitment to the date of expiring
Time frame: up to 18 months
The time from the date of recruitment to that of intracranial progression/failure noted on brain MRI or CT
Time frame: up to 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Derived from this study: PubMed 35096584Lin SY, Tsan DL, Chuang CC, Yang CC, Pai PC, Wang CL, Wu YM, Lee CC, Lin CH, Wei KC, Chou WC. Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan. Front Oncol. 2022 Jan 12;11:784635. doi: 10.3389/fonc.2021.784635. eCollection 2021.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hippocampal-sparing WBRT in people with Brain Metastasis and Brain Metastases, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 1 May 2023. 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 Taiwan. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chi-Cheng Chuang, M.D. (+886-33281200 ext. 2412, ccc2915@cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is delayed recall, as determined by the change/decline in verbal memory (WMS III- Word List score) from the baseline assessment to 4 months after the start of HS-WBRT. (time frame: 4 months after the start of HS-WBRT). The study lists 2 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 NCT03223675, which also lists 1 linked publication.
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 1 May 2023.