Brain MetastasesNCT06557187
Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for BMs of NSCLC
A study testing ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost in people with Brain Metastases and Non-small Cell Lung Cancer, run by Yatian Liu at 1 site in China.
Trial summary
WBRT (whole-brain radiation therapy) exhibits poor tumor control and decreased NCF (neurocognitive function). Herein, we investigated the safety and efficacy of HA-WBRT+SIB (hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost) in NSCLC (non-small cell lung cancer) with multiple brain… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Brain Metastases, Non-small Cell Lung Cancer
- What is being tested?
- ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2021to 1 Jan 2026
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults (aged 18-75 years) diagnosed with NSCLC, with a KPS (Karnofsky performance status) ≥70, at least four brain metastases visible on MRI (magnetic resonance imaging) outside a 5-mm margin around the bilateral hippocampi, not suitable for targeted therapy or progressing intracranial post targeted therapy.
Who cannot join
- Ineligible participants had a history of conditions affecting cognitive function (including mental illness, brain trauma, and Alzheimer\'s disease), other primary malignant tumors, uncontrolled systemic disease, uncontrolled extracranial sites of gross disease, and suitable for targeted therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for Multiple Brain Metastases in Non-small Cell Lung Cancer
WBRT (whole-brain radiation therapy) exhibits poor tumor control and decreased NCF (neurocognitive function). Herein, we investigated the safety and efficacy of HA-WBRT+SIB (hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost) in NSCLC (non-small cell lung cancer) with multiple brain metastases.We conducted a prospective, single-arm phase II trial administering HA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions) for multiple brain metastases (≥4) of NSCLC. Cognitive performance was assessed by the HVLT-R DR (Hopkins Verbal LearningTest-Revised delayed Recall).A-WBRT+SIB emerges as a promising and safe therapeutic, improving intracranial tumor control and protecting cognitive function in NSCLC with multiple brain metastases.
Read the detailed description
Lung cancer has high incidence and mortality rates. NSCLC is the most prevalent form accounting for 85% of all lung cancer cases with approximately 40% of individuals developing brain metastases during the illness. With advancements in therapies like targeted therapy and immunotherapy, the incidence of brain metastases have raised paralleled by a rise in survival rates of NSCLC. And NSCLC patients with brain metastases only 2 to 3 months of natural survival[6]. Therefore, it is urgent to improve the prognosis and intracranial control of NSCLC patients with brain metastases.
Brain metastases patients of NSCLC should be treated with local treatment on the basis of systemic treatment. For patients of NSCLC with brain metastases who are not suitable for targeted therapy or with progressing intracranial post targeted therapy, radiotherapy emerges as a significant therapeutic.Stereotactic radiosurgery (SRS) alone should be offered to patients with one to three unresected brain metastases for patients with asymptomatic brain metastases and no systemic therapy options.While the standard treatment for multiple brain metastases (≥4) remains controversial.
WBRT is used to be a common therapy in multiple brain metastases prolonging survival of patients to 6 months. But WBRT comes with neurotoxic effects, notably cognitive impairment affecting memory and learning. This cognitive decline is mainly attributed to hippocampal damage, a crucial region for learning and memory. The RTOG0933 and NRG Oncology CC001 trials have demonstrated that HA-WBRT effectively safeguards cognitive function and enhances the quality of life in patients with brain metastases. Furthermore, considering the tolerated dose of normal brain tissue, the dose of WBRT was low (30Gy/10F) with only 60% intracranial local control rate. The landmark RTOG9508 trial has demonstrated that WBRT in combination with boosted metastases can improve local intracranial control.
Prokic et al. reported that the simultaneous integrated boost during WBRT (WBRT+SIB) demonstrated superior hippocampal sparing and biological benefits of fractionation over sequential integrated boost. Advancements in radiotherapy techniqueshave led to the innovative HA-WBRT+SIB strategy, delivering higher dosages to existing metastases while minimizing radiation exposure to the hippocampus. However, evidence for the application of HA-WBRT+SIB in multiple (≥4) brain metastases of NSCLC remains insufficient. Therefore, this study aims to investigate the efficacy and safety of HA-WBRT+SIB in patients with multiple brain metastases of NSCLC.
- Conditions
- Brain Metastases, Non-small Cell Lung Cancer
- Being tested
- ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost
- Keywords
- brain metastases, hippocampus-avoidance, whole-brain radiation therapy, simultaneous integrated boost
- Medical subject headings
- Brain Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated BoostRadiation
hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost
| Study group | Role | What they receive |
|---|---|---|
| Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost | Experimental | HA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions) Receives: Radiation: ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intracranial local progression-free survival time (iLPFS)
determined as the time from HA-WBRT+SIB initiation to death, existing intracranial metastases progression, or last follow-up.
Measured: From date of enrollment until the date of progression of existing intracranial metastases or date of death from any cause, whichever came first, assessed up to 20 months
Secondary outcomes (5)
Intracranial progression-free survival time (iPFS)
measured from HA-WBRT+SIB initiation to existing or new metastases intracranial progression, death, or last follow-up.
Measured: From date of enrollment until the date of progression of existing or new metastases intracranial or date of death from any cause, whichever came first, assessed up to 20 months
Cognitive function
was measured by the relative change in HVLT-R DR score from the start of HA-WBRT+SIB to 4 months after the start of HA-WBRT+SIB.
Measured: From enrollment to the end of treatment at 4 weeks
OS (Overall survival)
described as the time from initiation of radiation to the last follow-up or death
Measured: From date of enrollment until the date of death from any cause, whichever came first, assessed up to 20 months
The cumulative incidence of local intracranial failure
measured as the progression of existing intracranial metastases
Measured: From date of enrollment until the date of progression of existing intracranial metastases， assessed up to 20 months
Cumulative incidence of intracranial failure
described as the progression of existing or new intracerebral metastases.
Measured: From date of enrollment until the date of the progression of existing or new intracerebral metastases assessed up to 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2024
- Study start1 Jan 2021
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jan 2026 (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
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yatian Liu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yatian Liu, Jiangsu Cancer Institute & Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06557187
- Sponsor's protocol ID
- JZ233490202001088
- Other IDs
- 100000RMB
- Status last verified
- Mar 2025
- First submitted
- 13 Aug 2024
- Last updated
- 18 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The results of the study have not been published
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost for Multiple Brain Metastases in Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06557187
- Acronym / sponsor ID
- JZ233490202001088
- Conditions
- Brain Metastases, Non-small Cell Lung Cancer
- Keywords
- brain metastases, hippocampus-avoidance, whole-brain radiation therapy, simultaneous integrated boost
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Yatian LiuUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 16 Aug 2024 (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.
WBRT (whole-brain radiation therapy) exhibits poor tumor control and decreased NCF (neurocognitive function). Herein, we investigated the safety and efficacy of HA-WBRT+SIB (hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost) in NSCLC (non-small cell lung cancer) with multiple brain metastases.We conducted a prospective, single-arm phase II trial administering HA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions) for multiple brain metastases (≥4) of NSCLC. Cognitive performance was assessed by the HVLT-R DR (Hopkins Verbal LearningTest-Revised delayed Recall).A-WBRT+SIB emerges as a promising and safe therapeutic, improving intracranial tumor control and protecting cognitive function in NSCLC with multiple brain metastases.
Detailed description
Lung cancer has high incidence and mortality rates. NSCLC is the most prevalent form accounting for 85% of all lung cancer cases with approximately 40% of individuals developing brain metastases during the illness. With advancements in therapies like targeted therapy and immunotherapy, the incidence of brain metastases have raised paralleled by a rise in survival rates of NSCLC. And NSCLC patients with brain metastases only 2 to 3 months of natural survival[6]. Therefore, it is urgent to improve the prognosis and intracranial control of NSCLC patients with brain metastases.
Brain metastases patients of NSCLC should be treated with local treatment on the basis of systemic treatment. For patients of NSCLC with brain metastases who are not suitable for targeted therapy or with progressing intracranial post targeted therapy, radiotherapy emerges as a significant therapeutic.Stereotactic radiosurgery (SRS) alone should be offered to patients with one to three unresected brain metastases for patients with asymptomatic brain metastases and no systemic therapy options.While the standard treatment for multiple brain metastases (≥4) remains controversial.
WBRT is used to be a common therapy in multiple brain metastases prolonging survival of patients to 6 months. But WBRT comes with neurotoxic effects, notably cognitive impairment affecting memory and learning. This cognitive decline is mainly attributed to hippocampal damage, a crucial region for learning and memory. The RTOG0933 and NRG Oncology CC001 trials have demonstrated that HA-WBRT effectively safeguards cognitive function and enhances the quality of life in patients with brain metastases. Furthermore, considering the tolerated dose of normal brain tissue, the dose of WBRT was low (30Gy/10F) with only 60% intracranial local control rate. The landmark RTOG9508 trial has demonstrated that WBRT in combination with boosted metastases can improve local intracranial control.
Prokic et al. reported that the simultaneous integrated boost during WBRT (WBRT+SIB) demonstrated superior hippocampal sparing and biological benefits of fractionation over sequential integrated boost. Advancements in radiotherapy techniqueshave led to the innovative HA-WBRT+SIB strategy, delivering higher dosages to existing metastases while minimizing radiation exposure to the hippocampus. However, evidence for the application of HA-WBRT+SIB in multiple (≥4) brain metastases of NSCLC remains insufficient. Therefore, this study aims to investigate the efficacy and safety of HA-WBRT+SIB in patients with multiple brain metastases of NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost | Experimental | Radiation: ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated BoostHA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adults (aged 18-75 years) diagnosed with NSCLC, with a KPS (Karnofsky performance status) ≥70, at least four brain metastases visible on MRI (magnetic resonance imaging) outside a 5-mm margin around the bilateral hippocampi, not suitable for targeted therapy or progressing intracranial post targeted therapy.
Key exclusion criteria (1 listed)
- Ineligible participants had a history of conditions affecting cognitive function (including mental illness, brain trauma, and Alzheimer\'s disease), other primary malignant tumors, uncontrolled systemic disease, uncontrolled extracranial sites of gross disease, and suitable for targeted therapy.
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 |
|---|---|---|
| ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boosthippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost | Radiation | Hippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost |
Primary outcome
Intracranial local progression-free survival time (iLPFS)
Time frame: From date of enrollment until the date of progression of existing intracranial metastases or date of death from any cause, whichever came first, assessed up to 20 months
determined as the time from HA-WBRT+SIB initiation to death, existing intracranial metastases progression, or last follow-up.
5 secondary outcomes
Intracranial progression-free survival time (iPFS)
Time frame: From date of enrollment until the date of progression of existing or new metastases intracranial or date of death from any cause, whichever came first, assessed up to 20 months
Cognitive function
Time frame: From enrollment to the end of treatment at 4 weeks
OS (Overall survival)
Time frame: From date of enrollment until the date of death from any cause, whichever came first, assessed up to 20 months
The cumulative incidence of local intracranial failure
Time frame: From date of enrollment until the date of progression of existing intracranial metastases， assessed up to 20 months
Cumulative incidence of intracranial failure
Time frame: From date of enrollment until the date of the progression of existing or new intracerebral metastases assessed up to 20 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 18 Apr 2025.
- Individual participant dataSharing planned: No. The results of the study have not been published
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ippocampus-Avoidance Whole-Brain Radiation Therapy With Simultaneous Integrated Boost in people with Brain Metastases and Non-small Cell Lung Cancer, run by Yatian Liu at 1 site in China.
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 1 inclusion and 1 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 18 Apr 2025. 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 China. 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?
Intracranial local progression-free survival time (iLPFS) (time frame: From date of enrollment until the date of progression of existing intracranial metastases or date of death from any cause, whichever came first, assessed up to 20 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 18 Apr 2025.