SCLC,Extensive StagePhase 1/2NCT06243003
WBRT With Hippocampal-avoidance Technique Followed by SRT for Extensive-stage SCLC With Baseline Brain Metastases
A Phase 1/2 study testing HA-WBRT plus SBRT in people with SCLC,Extensive Stage and Brain Metastases, run by Fudan University at 1 site in China.
Trial summary
This study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS as first-line treatment for SCLC patients with brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SCLC,Extensive Stage, Brain Metastases
- What is being tested?
- HA-WBRT plus SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteChina
- Study dates
- 15 Jan 2024to Dec 2026
- Phase
- Phase 1/2
- 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
- Eastern Cooperative Oncology Group(ECOG) performance status score 0-2;
- Small cell lung cancer confirmed by histopathology or cytology;
- Complete baseline imaging data (including brain enhanced MRI/CT, positron emission tomography(PET/CT) or chest enhanced CT+ bone scan + neck and abdomen B ultrasound /CT) should be obtained before first-line treatment;
- Patients with initial diagnosis of ES-SCLC with brain metastases who planned to receive at least 4 cycles of standard platinum-based doublet chemotherapy combined with immunotherapy (PD-1 or PD-L1 monoclonal antibody) as first-line treatment, and who met the organ function requirements as judged by the investigator;
- Brain metastases assessed by contrast-enhanced MRI met the criteria for SRS (less than or equal to 10 brain metastases, maximum tumor volume less than 10ml, maximum tumor diameter less than 3cm, total tumor volume less than 15ml, and no evidence of leptomeningeal metastasis).
- No history of other malignant tumors;
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- Male/female of childbearing age agreed to use contraception (surgical ligation or oral contraceptive/intrauterine device + condom) during the trial;
- Life expectancy ≥3 months
- Patients must be able to understand and voluntarily sign informed consent.
Who cannot join
- Patients with non-small cell lung cancer (NSCLC) components on baseline pathological examination;
- Patients who had received any antitumor therapy prior to ES-SCLC diagnosis;
- Patients with imaging evidence of leptomeningeal metastasis or suspected leptomeningeal metastasis with symptoms and signs;
- patients unable to undergo contrast-enhanced MRI;
- Patients with severe symptoms of brain metastases requiring emergency surgery to reduce intracranial pressure;
- Patients who could not complete immobilization for radiotherapy or tolerate radiotherapy;
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- Symptomatic interstitial lung disease or active infectious/noninfectious pneumonia;
- Patients requiring long-term corticosteroid or immunosuppressive therapy;
- Patients who are allergic to PD-1 or PD-L1 monoclonal antibody immunotherapy or unable to receive immune maintenance therapy for other reasons;
- Lactating or pregnant women;
- The patient had severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.
- Medical examination or clinical findings or other uncontrollable conditions that the investigator considers may interfere with the results or increase the risk of treatment complications for the patient;
- Patients with mental illness, substance abuse, or social problems that could affect adherence were excluded from enrollment after physician review.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai
Zhengfei Zhu, MD, +86-18017312901, fuscczzf@163.com
Xiao Chu, +86-18017317922, chuxiao@sibs.ac.cn
About this study
Official title: A Phase I/II Study to Evaluate the Safety and Efficacy of Hippocampal-avoidance Whole Brain Radiotherapy Followed by Stereotactic Radiotherapy for Extensive-stage Small Cell Lung Cancer With Baseline Brain Metastases
This study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS as first-line treatment for SCLC patients with brain metastases.
Read the detailed description
At present, the standard treatment for SCLC brain metastases is whole brain radiotherapy (WBRT). However, WBRT is palliative in nature due to its low dose and poor long-term control rate of intracranial lesions. At the same time, with the advent of the era of immunotherapy, a variety of PD-1/PD-L1 monoclonal antibodies combined with chemotherapy have become the standard first-line treatment for extensive-stage SCLC(ES-SCLC). Studies have shown that the survival time of SCLC patients with brain metastases is expected to be further prolonged in the era of chemotherapy and immunotherapy. Therefore, it is particularly important to further improve the control rate of intracranial lesions.
It has been confirmed in previous studies that WBRT combined with stereotactic radiotherapy for visible intracranial lesions (SRS/SRT) can effectively improve the control rate of intracranial lesions. However, most of the previous studies of WBRT combined with SRT for brain metastases did not include or only included a very small number of patients with SCLC. Studies on thoracic radiotherapy for limited-stage small cell lung cancer have found that an increase in radiotherapy dose can significantly improve the prognosis of patients with SCLC, which was previously considered to be highly radiosensitive. It is reasonable to think that SRS combined with WBRT for SCLC brain metastases may improve the prognosis of patients.
WBRT is known to cause severe cognitive impairment, which has also led to the reluctance of some patients to undergo WBRT. In the era of chemotherapy, the NRG-CC001 study showed that Hippocampal avoidance WBRT (HA-WBRT) could better protect the cognitive function of patients without affecting the prognosis of patients. The 2022 ASTRO guidelines have clearly recommended the use of hippocampal protection techniques in WBRT. Considering the lack of previous literature on the use of SRS combined with WBRT in SCLC patients in the chemo-immunotherapy era, The aim of this study is to adopt the dose fractionation of SRS combined with WBRT, which has been proven to be safe in the treatment of brain metastases from NSCLC, and to evaluate the safety of this treatment mode in SCLC patients with brain metastases receiving standard first-line chemoimmunotherapy.
In summary, this study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS in the first-line treatment of SCLC patients with baseline brain metastases who are suitable for SRS treatment during the standard first-line chemotherapy combined with immunotherapy.
- Conditions
- SCLC,Extensive Stage, Brain Metastases
- Being tested
- HA-WBRT plus SBRT
- Keywords
- whole brain radiotherapy (WBRT), stereotactic body radiotherapy (SBRT)
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HA-WBRT plus SBRTRadiation
hippocampal-avoidance whole brain radiotherapy (WBRT) followed by stereotactic body radiotherapy (SBRT)
| Study group | Role | What they receive |
|---|---|---|
| HA-WBRT with SRS | Experimental | hippocampal-sparing WBRT combined with SRS will be used to treat SCLC patients with baseline brain metastases during standard first-line chemotherapy combined with immunotherapy. Receives: Radiation: HA-WBRT plus SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
dose-limiting toxicities rate
dose-limiting toxicities(DLTs) were assessed according to CTCAE 5.0 criteria and included the following three conditions, with the exception of asymptomatic biochemical abnormalities: (1) grade 3 toxicity lasting for more than 7 consecutive days; (2) Grade 4 toxicity excluding neutropenia and thrombocytopenia; (3) Treatment-related grade 5 adverse events could not be excluded.
Measured: 30 days since the final day of radiotherapy
1-year intracranial progression-free survival rate
1-year intracranial progression-free survival (iPFS) rate was defined as proportion of patients without intracranial disease progression or death at 1 year of follow-up
Measured: one year
Secondary outcomes (4)
overall survival
overall survival(OS) was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.
Measured: one year
time to intracranial progression
Time to intracranial progression was defined as the time from enrollment for treatment to the observation of progression of intracranial disease.
Measured: one year
Changes in learning and memory function
learning and memory function was assessed at 2, 4, 6, and 12 months from the first day of radiotherapy using the Hopkins Verbal Learning Test (HVLT-R)
Measured: one year
processing speed and executive function
processing speed and executive function was assessed at 2, 4, 6, and 12 months from the first day of radiotherapy using the trail making test (TMT-Part A, to assess processing speed, and TMT-Part B, to assess executive function).
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2024
- Study start15 Jan 2024
- Primary completionJul 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCLC,Extensive StageStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- For ES-SCLC patients with baseline brain metastasis enrolled in this study, standard chemo-immunotherapy will be delivered every 3 weeks. Simulation for radiotherapy should be performed at baseline, and WBRT should be completed no later than the start of the third course of systemic treatment. The WBRT dose is 30Gy/10Fx. For patients without brain metastases within 1cm of the hippocampus, hippocampal avoidance technology should be employed. After WBRT, the treating physician will perform another simulation for subsequent SRS treatment to the brain lesions. SRS should be completed no later than the start of the fourth course of drug treatment. Specific SRS dose should be as follows: 16Gy for tumors with a diameter ≤ 2cm; 12Gy for tumors with a diameter of between 2cm and 3cm. WBRT and SRS should be performed during the interval between two systemic drug treatments, concurrent (on the same day) brain radiotherapy with chemo-immunotherapy treatment should be avoided.
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhengfei Zhu, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06243003
- Sponsor's protocol ID
- SCLC-BRT
- Status last verified
- Feb 2024
- First submitted
- 24 Jan 2024
- Last updated
- 7 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study to Evaluate the Safety and Efficacy of Hippocampal-avoidance Whole Brain Radiotherapy Followed by Stereotactic Radiotherapy for Extensive-stage Small Cell Lung Cancer With Baseline Brain Metastases
- ClinicalTrials.gov ID
- NCT06243003
- Acronym / sponsor ID
- SCLC-BRT
- Conditions
- SCLC,Extensive Stage, Brain Metastases
- Keywords
- whole brain radiotherapy (WBRT), stereotactic body radiotherapy (SBRT)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 5 Feb 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.
This study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS as first-line treatment for SCLC patients with brain metastases.
Detailed description
At present, the standard treatment for SCLC brain metastases is whole brain radiotherapy (WBRT). However, WBRT is palliative in nature due to its low dose and poor long-term control rate of intracranial lesions. At the same time, with the advent of the era of immunotherapy, a variety of PD-1/PD-L1 monoclonal antibodies combined with chemotherapy have become the standard first-line treatment for extensive-stage SCLC(ES-SCLC). Studies have shown that the survival time of SCLC patients with brain metastases is expected to be further prolonged in the era of chemotherapy and immunotherapy. Therefore, it is particularly important to further improve the control rate of intracranial lesions.
It has been confirmed in previous studies that WBRT combined with stereotactic radiotherapy for visible intracranial lesions (SRS/SRT) can effectively improve the control rate of intracranial lesions. However, most of the previous studies of WBRT combined with SRT for brain metastases did not include or only included a very small number of patients with SCLC. Studies on thoracic radiotherapy for limited-stage small cell lung cancer have found that an increase in radiotherapy dose can significantly improve the prognosis of patients with SCLC, which was previously considered to be highly radiosensitive. It is reasonable to think that SRS combined with WBRT for SCLC brain metastases may improve the prognosis of patients.
WBRT is known to cause severe cognitive impairment, which has also led to the reluctance of some patients to undergo WBRT. In the era of chemotherapy, the NRG-CC001 study showed that Hippocampal avoidance WBRT (HA-WBRT) could better protect the cognitive function of patients without affecting the prognosis of patients. The 2022 ASTRO guidelines have clearly recommended the use of hippocampal protection techniques in WBRT. Considering the lack of previous literature on the use of SRS combined with WBRT in SCLC patients in the chemo-immunotherapy era, The aim of this study is to adopt the dose fractionation of SRS combined with WBRT, which has been proven to be safe in the treatment of brain metastases from NSCLC, and to evaluate the safety of this treatment mode in SCLC patients with brain metastases receiving standard first-line chemoimmunotherapy.
In summary, this study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS in the first-line treatment of SCLC patients with baseline brain metastases who are suitable for SRS treatment during the standard first-line chemotherapy combined with immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- For ES-SCLC patients with baseline brain metastasis enrolled in this study, standard chemo-immunotherapy will be delivered every 3 weeks. Simulation for radiotherapy should be performed at baseline, and WBRT should be completed no later than the start of the third course of systemic treatment. The WBRT dose is 30Gy/10Fx. For patients without brain metastases within 1cm of the hippocampus, hippocampal avoidance technology should be employed. After WBRT, the treating physician will perform another simulation for subsequent SRS treatment to the brain lesions. SRS should be completed no later than the start of the fourth course of drug treatment. Specific SRS dose should be as follows: 16Gy for tumors with a diameter ≤ 2cm; 12Gy for tumors with a diameter of between 2cm and 3cm. WBRT and SRS should be performed during the interval between two systemic drug treatments, concurrent (on the same day) brain radiotherapy with chemo-immunotherapy treatment should be avoided.
| Arm | Type | Receives |
|---|---|---|
| HA-WBRT with SRS | Experimental | Radiation: HA-WBRT plus SBRThippocampal-sparing WBRT combined with SRS will be used to treat SCLC patients with baseline brain metastases during standard first-line chemotherapy combined with immunotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Eastern Cooperative Oncology Group(ECOG) performance status score 0-2;
- Small cell lung cancer confirmed by histopathology or cytology;
- Complete baseline imaging data (including brain enhanced MRI/CT, positron emission tomography(PET/CT) or chest enhanced CT+ bone scan + neck and abdomen B ultrasound /CT) should be obtained before first-line treatment;
- Patients with initial diagnosis of ES-SCLC with brain metastases who planned to receive at least 4 cycles of standard platinum-based doublet chemotherapy combined with immunotherapy (PD-1 or PD-L1 monoclonal antibody) as first-line treatment, and who met the organ function requirements as judged by the investigator;
- Brain metastases assessed by contrast-enhanced MRI met the criteria for SRS (less than or equal to 10 brain metastases, maximum tumor volume less than 10ml, maximum tumor diameter less than 3cm, total tumor volume less than 15ml, and no evidence of leptomeningeal metastasis).
Key exclusion criteria (13 listed)
- Patients with non-small cell lung cancer (NSCLC) components on baseline pathological examination;
- Patients who had received any antitumor therapy prior to ES-SCLC diagnosis;
- Patients with imaging evidence of leptomeningeal metastasis or suspected leptomeningeal metastasis with symptoms and signs;
- patients unable to undergo contrast-enhanced MRI;
- Patients with severe symptoms of brain metastases requiring emergency surgery to reduce intracranial pressure;
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 |
|---|---|---|
| HA-WBRT plus SBRThippocampal-avoidance whole brain radiotherapy (WBRT) followed by stereotactic body radiotherapy (SBRT) | Radiation | HA-WBRT with SRS |
Primary outcome
dose-limiting toxicities rate
Time frame: 30 days since the final day of radiotherapy
dose-limiting toxicities(DLTs) were assessed according to CTCAE 5.0 criteria and included the following three conditions, with the exception of asymptomatic biochemical abnormalities: (1) grade 3 toxicity lasting for more than 7 consecutive days; (2) Grade 4 toxicity excluding neutropenia and thrombocytopenia; (3) Treatment-related grade 5 adverse events could not be excluded.
1-year intracranial progression-free survival rate
Time frame: one year
1-year intracranial progression-free survival (iPFS) rate was defined as proportion of patients without intracranial disease progression or death at 1 year of follow-up
4 secondary outcomes
overall survival
Time frame: one year
time to intracranial progression
Time frame: one year
Changes in learning and memory function
Time frame: one year
processing speed and executive function
Time frame: one year
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 7 Feb 2024.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HA-WBRT plus SBRT in people with SCLC,Extensive Stage and Brain Metastases, run by Fudan University 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 9 inclusion and 13 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 7 Feb 2024. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 zhengfei zhu (+8618017312901, fuscczzf@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
dose-limiting toxicities rate (time frame: 30 days since the final day of radiotherapy). 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 7 Feb 2024.