Brain OligometastasesNCT05807165
HF-SRT vs. HS-WBRT in Treating Patients With Brain Oligometastases
An observational study of Brain Oligometastases, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
[Background] For newly-diagnosed patients with brain metastases (BMs), conventional whole-brain radiotherapy (WBRT) might still remain a common palliative management. However, WBRT-related late consequences, particularly a decline in neurocognitive functions (NCFs), are a major concern. Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- Brain Oligometastases
- What is being tested?
- Hypofractionated Stereotactic Radiotherapy (HF-SRT) and Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantine
- Type of treatment
- Surgery or procedure
- How many people
- 115 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2023to 31 Jul 2026
- Phase
- Observational
- 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 85 years
- All sexes
- Adult, Older adult
Study population: Patients with newly-diagnosed brain oligometastases and an acceptable performance status would receive baseline neurocognitive assessment.
Who may be able to join
- Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for postoperative adjuvant or therapeutic hypofractionated stereotactic radiotherapy (HF-SRT)
- A Fair/good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or an acceptable performance 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 4 cm shown on pre-radiotherapy MRI; namely, that is the clinical setting of oligometastatic brain disease or brain oligometastases
Who cannot join
- Patients with their primary cancer arising from hematological malignancies (i.e., malignant lymphomas, leukemia), germ cell tumors, or malignant meningiomas
- Patients with MRI-identified metastasis within 5 mm peri-hippocampally
- Patients with metastasis involving the brain stem
- Clinical suspicion of leptomeningeal spreading
- History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hypofractionated Stereotactic Radiotherapy Versus Hippocampus-sparing Whole-brain Radiotherapy in Treating Cancer Patients With Brain Oligometastases: A Phase II Parallel Non-randomized and Prospective Observational Study
[Background] For newly-diagnosed patients with brain metastases (BMs), conventional whole-brain radiotherapy (WBRT) might still remain a common palliative management. However, WBRT-related late consequences, particularly a decline in neurocognitive functions (NCFs), are a major concern. Actually, WBRT-related neurocognitive dysfunction is usually characterized as deterioration involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role.
To postpone the occurrence and mitigate neurocognitive impairments associated with conventional WBRT, there have been some strategies in the clinical practice of radiation oncology. Among them, the technology/technique of highly precise/accurate stereotactic radiosurgery or stereotactic radiotherapy (i.e., hypofractionated stereotactic radiotherapy, HS-SRT) might have been widely administered in irradiating exclusively the focal brain metastatic lesions, particularly in cancer patients with a limited number of brain metastases. By contrast, the planning strategy of hippocampus avoidance during the course of whole-brain irradiation has also been well-established in preserving NCFs.
Read more
[Methods] Newly-diagnosed cancer patients harboring 1 - 4 brain metastatic lesions are eligible if they still have fair/good performance status. Eligible and enrolled should receive baseline brain MRI examination and pre-WBRT neurocognitive assessment. Although non-randomized, this phase II trial comprises two prospective (radiotherapeutic) cohorts with individually different planning techniques and prescription schedules. Cohort I represents patients referred for arranging partial-brain irradiation; namely, a course of hypofractionated stereotactic radiotherapy (HF-SRT) is delivered within 2 weeks with a cumulative dose of 3000 - 3500 cGy in 5 fractions. By contrast, Cohort II stands for patients referred for arranging the course of hippocampus-sparing WBRT (HS-WBRT), delivered within 3 weeks with a cumulative dose of 3000 cGy in 12 fractions, during which the planning technique of simultaneous integrated boost (SIB) is employed to focally escalate the dose irradiating the brain metastatic foci. Besides, adhering to several international clinical practice guidelines, the synergic use of the neuroprotective agent (memantine) will be routinely applied in the treatment Cohort II (HS-WBRT). In both treatment cohorts, 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 neurocognitive functions.
The primary outcome measure is the median time of CNS progression-free survival (CNS-PFS). Secondary outcome measures encompass both neuro-oncological endpoints and neurocognitive endpoints, among which there is cognitive-deterioration-free survival (CD-free survival). CD-free survival is defined mainly as the time from enrollment to a NCF decline of exceeding than 1 SD away from the baseline involving at least one of the assessed NCF tests. Additionally, patients who expire before 6 months or are alive but fail to undergo all the neurocognitive testing administered would also be defined as suffering from cognitive deterioration.
[Expected results] This prospective observational study aims to examine thoroughly and analyze the comparatively between the two radiotherapeutic cohorts (HF-SRT versus HS-WBRT), addressing both CNS tumor control and neurocognitive functional outcomes. It is expected that the patterns of (CNS) failure and individual time to progression will be clearly demonstrated in this prospective observational study encompassing two distinct radiotherapeutic cohorts.
- Conditions
- Brain Oligometastases
- Being tested
- Hypofractionated Stereotactic Radiotherapy (HF-SRT), Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantine
- Keywords
- Brain Oligometastases, Stereotactic Radiotherapy (SRT), Hypofractionation, Hypofractionated Stereotactic Radiotherapy (HF-SRT), Hippocampus, Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT), Neurocognitive Functions (NCFs), Central Nervous System (CNS), Progression-free Survival (PFS), CNS Progression-Free Survival (CNS-PFS), Patterns of CNS Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypofractionated Stereotactic Radiotherapy (HF-SRT)Radiation
The administered dose-fractionation schemes range between 30 and 35 Gy delivered within two weeks with a dose per fractionation ranging from 6 to 7 Gy.
Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantineRadiation
- The prescribed dose is 30 Gy delivered in 12 fractions for therapeutic or adjuvant WBRT.
- The prescription of memantine for finally twice-daily dosing will be prescribed as follows:
- During the first 3 weeks concurrent with the delivery of hippocampus-sparing WBRT, 5-mg morning dose will be initially prescribed [Week 1 -3]
- 5-mg twice a day in the following week [Week 4]
- A morning dose of 10 mg and an evening dose of 5 mg in the following week [Week 5]
- 10-mg twice a day for the subsequent weeks up to Week 24 [Week 6 - 24]
| Study group | Role | What they receive |
|---|---|---|
| HF-SRT | RT techniques and the dose schemes in the cohort of Hypofractionated Stereotactic Radiotherapy (HF-SRT) Receives: Radiation: Hypofractionated Stereotactic Radiotherapy (HF-SRT) | |
| HS-WBRT plus memantine | The course of hippocampus-sparing whole-brain radiotherapy (HS-WBRT) combined with the synergic use of the neuroprotective agent, memantine Receives: Radiation: Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
CNS progression-free survival (CNS-PFS)
The median CNS progression-free survival (CNS-PFS), which is a time-dependent endpoint, defined as the time from study enrollment to CNS disease progression of death from any cause.
Measured: The time from study enrollment to CNS disease progression of death from any cause, assessed up to 10 years.
Cognitive-deterioration-free survival (CD-free survival)
The time from enrollment to a cognitive decline of exceeding more than 1SD away from the baseline in at least one of the assessed NCF tests. Furthermore, regarding cognitive-deterioration-free survival, patients who expire before 6 months or are alive but do not undergo all the neurocognitive testing administered or even fail to receive MMSE evaluation would be assumed reasonably that they suffer cognitive deterioration at the time of death or at the time point, or they fail to receive their first neurocognitive assessment follow-up as long as there are no subsequent NCF assessments.
Measured: The time from enrollment to a cognitive decline of exceeding more than 1SD away from the baseline in at least one of the assessed NCF tests, assessed up to 24 months.
Secondary outcomes (6)
Overall survival (OS)
Measured: The time from enrollment to death, assessed up to 10 years.
Median survival time (MST)
Measured: The time from enrollment to death, assessed up to 10 years.
Causes of death (neurologic vs non-neurologic death)
Measured: The time from enrollment to death, assessed up to 10 years.
Patterns of CNS (Intracranial or Leptomeningeal Disease) failure evaluated through brain MRI
Three patterns of central nervous system (CNS) failure were classified particularly when the CNS progression in the corresponding patient manifests for the first time after the course of HF-SRT: intracranial local failure (LF), distant brain parenchymal failure (DPF), and development of leptomeningeal disease (LMD).
Measured: The time from enrollment to CNS failure, assessed up to 10 years.
Time to progression (TTP)
Time to CNS progression
Measured: The time from enrollment to CNS progression, assessed up to 10 years.
Progression-free survival (PFS)
Intracranial PFS or CNS progression-free survival; CNS progression-free survival
Measured: The time from enrollment to disease progression, assessed up to 10 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2023
- Study start1 Aug 2023 (estimated)
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain OligometastasesStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 115 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
- NCT05807165
- Sponsor's protocol ID
- 202201915A3
- Status last verified
- Dec 2022
- First submitted
- 5 Mar 2023
- Last updated
- 11 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypofractionated Stereotactic Radiotherapy Versus Hippocampus-sparing Whole-brain Radiotherapy in Treating Cancer Patients With Brain Oligometastases: A Phase II Parallel Non-randomized and Prospective Observational Study
- ClinicalTrials.gov ID
- NCT05807165
- Acronym / sponsor ID
- 202201915A3
- Conditions
- Brain Oligometastases
- Keywords
- Brain Oligometastases, Stereotactic Radiotherapy (SRT), Hypofractionation, Hypofractionated Stereotactic Radiotherapy (HF-SRT), Hippocampus, Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT), Neurocognitive Functions (NCFs), Central Nervous System (CNS)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 115 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 1 Aug 2023 (estimated)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Jul 2026 (estimated)
- First posted
- 11 Apr 2023 (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.
[Background] For newly-diagnosed patients with brain metastases (BMs), conventional whole-brain radiotherapy (WBRT) might still remain a common palliative management. However, WBRT-related late consequences, particularly a decline in neurocognitive functions (NCFs), are a major concern. Actually, WBRT-related neurocognitive dysfunction is usually characterized as deterioration involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role.
To postpone the occurrence and mitigate neurocognitive impairments associated with conventional WBRT, there have been some strategies in the clinical practice of radiation oncology. Among them, the technology/technique of highly precise/accurate stereotactic radiosurgery or stereotactic radiotherapy (i.e., hypofractionated stereotactic radiotherapy, HS-SRT) might have been widely administered in irradiating exclusively the focal brain metastatic lesions, particularly in cancer patients with a limited number of brain metastases. By contrast, the planning strategy of hippocampus avoidance during the course of whole-brain irradiation has also been well-established in preserving NCFs.
[Methods] Newly-diagnosed cancer patients harboring 1 - 4 brain metastatic lesions are eligible if they still have fair/good performance status. Eligible and enrolled should receive baseline brain MRI examination and pre-WBRT neurocognitive assessment. Although non-randomized, this phase II trial comprises two prospective (radiotherapeutic) cohorts with individually different planning techniques and prescription schedules. Cohort I represents patients referred for arranging partial-brain irradiation; namely, a course of hypofractionated stereotactic radiotherapy (HF-SRT) is delivered within 2 weeks with a cumulative dose of 3000 - 3500 cGy in 5 fractions. By contrast, Cohort II stands for patients referred for arranging the course of hippocampus-sparing WBRT (HS-WBRT), delivered within 3 weeks with a cumulative dose of 3000 cGy in 12 fractions, during which the planning technique of simultaneous integrated boost (SIB) is employed to focally escalate the dose irradiating the brain metastatic foci. Besides, adhering to several international clinical practice guidelines, the synergic use of the neuroprotective agent (memantine) will be routinely applied in the treatment Cohort II (HS-WBRT). In both treatment cohorts, 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 neurocognitive functions.
The primary outcome measure is the median time of CNS progression-free survival (CNS-PFS). Secondary outcome measures encompass both neuro-oncological endpoints and neurocognitive endpoints, among which there is cognitive-deterioration-free survival (CD-free survival). CD-free survival is defined mainly as the time from enrollment to a NCF decline of exceeding than 1 SD away from the baseline involving at least one of the assessed NCF tests. Additionally, patients who expire before 6 months or are alive but fail to undergo all the neurocognitive testing administered would also be defined as suffering from cognitive deterioration.
[Expected results] This prospective observational study aims to examine thoroughly and analyze the comparatively between the two radiotherapeutic cohorts (HF-SRT versus HS-WBRT), addressing both CNS tumor control and neurocognitive functional outcomes. It is expected that the patterns of (CNS) failure and individual time to progression will be clearly demonstrated in this prospective observational study encompassing two distinct radiotherapeutic cohorts.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HF-SRT | – | Radiation: Hypofractionated Stereotactic Radiotherapy (HF-SRT)RT techniques and the dose schemes in the cohort of Hypofractionated Stereotactic Radiotherapy (HF-SRT) |
| HS-WBRT plus memantine | – | Radiation: Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantineThe course of hippocampus-sparing whole-brain radiotherapy (HS-WBRT) combined with the synergic use of the neuroprotective agent, memantine |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients with newly-diagnosed brain oligometastases and an acceptable performance status would receive baseline neurocognitive assessment.
Key inclusion criteria (3 listed)
- Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for postoperative adjuvant or therapeutic hypofractionated stereotactic radiotherapy (HF-SRT)
- A Fair/good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or an acceptable performance 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 4 cm shown on pre-radiotherapy MRI; namely, that is the clinical setting of oligometastatic brain disease or brain oligometastases
Key exclusion criteria (5 listed)
- Patients with their primary cancer arising from hematological malignancies (i.e., malignant lymphomas, leukemia), germ cell tumors, or malignant meningiomas
- Patients with MRI-identified metastasis within 5 mm peri-hippocampally
- Patients with metastasis involving the brain stem
- Clinical suspicion of leptomeningeal spreading
- 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 |
|---|---|---|
| Hypofractionated Stereotactic Radiotherapy (HF-SRT)The administered dose-fractionation schemes range between 30 and 35 Gy delivered within two weeks with a dose per fractionation ranging from 6 to 7 Gy. | Radiation | HF-SRT |
| Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantine* The prescribed dose is 30 Gy delivered in 12 fractions for therapeutic or adjuvant WBRT. * The prescription of memantine for finally twice-daily dosing will be prescribed as follows: * During the first 3 weeks concurrent with the delivery of hippocampus-sparing WBRT, 5-mg morning dose will be initially prescribed [Week 1 -3] * 5-mg twice a day in the following week [Week 4] * A morning dose of 10 mg and an evening dose of 5 mg in the following week [Week 5] * 10-mg twice a day for the subsequent weeks up to Week 24 [Week 6 - 24] | Radiation | HS-WBRT plus memantine |
Primary outcome
CNS progression-free survival (CNS-PFS)
Time frame: The time from study enrollment to CNS disease progression of death from any cause, assessed up to 10 years.
The median CNS progression-free survival (CNS-PFS), which is a time-dependent endpoint, defined as the time from study enrollment to CNS disease progression of death from any cause.
Cognitive-deterioration-free survival (CD-free survival)
Time frame: The time from enrollment to a cognitive decline of exceeding more than 1SD away from the baseline in at least one of the assessed NCF tests, assessed up to 24 months.
The time from enrollment to a cognitive decline of exceeding more than 1SD away from the baseline in at least one of the assessed NCF tests. Furthermore, regarding cognitive-deterioration-free survival, patients who expire before 6 months or are alive but do not undergo all the neurocognitive testing administered or even fail to receive MMSE evaluation would be assumed reasonably that they suffer cognitive deterioration at the time of death or at the time point, or they fail to receive their first neurocognitive assessment follow-up as long as there are no subsequent NCF assessments.
6 secondary outcomes
Overall survival (OS)
Time frame: The time from enrollment to death, assessed up to 10 years.
Median survival time (MST)
Time frame: The time from enrollment to death, assessed up to 10 years.
Causes of death (neurologic vs non-neurologic death)
Time frame: The time from enrollment to death, assessed up to 10 years.
Patterns of CNS (Intracranial or Leptomeningeal Disease) failure evaluated through brain MRI
Time frame: The time from enrollment to CNS failure, assessed up to 10 years.
Time to progression (TTP)
Time frame: The time from enrollment to CNS progression, assessed up to 10 years.
Progression-free survival (PFS)
Time frame: The time from enrollment to disease progression, assessed up to 10 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2023.
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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?
An observational study of Brain Oligometastases, 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 11 Apr 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 Din-Li Tsan, M.D. (886-33281200 ext. 7172, vottale@cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CNS progression-free survival (CNS-PFS) (time frame: The time from study enrollment to CNS disease progression of death from any cause, assessed up to 10 years.). 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?
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 11 Apr 2023.