NSCLC Stage IVPhase 2NCT06501391
Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable Brain Metastasis
A Phase 2 study testing PD-L1/PD-1 inhibitor and chemotherapy and SRT or WBRT in people with NSCLC Stage IV and Brain Metastases, run by Fudan University at 1 site in China.
Trial summary
Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC Stage IV, Brain Metastases
- What is being tested?
- PD-L1/PD-1 inhibitor and chemotherapy and SRT or WBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2024to Jul 2027
- Phase
- Phase 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
- Age ≥ 18 years;
- KPS score ≥ 70;
- Negative genetic testing for common driver genes including EGFR, ALK, ROS-1;
- Pathologically confirmed non-small cell lung cancer;
- Clinical stage IV (AJCC, 8th edition, 2017);
- Diagnosed with brain metastasis at the time of diagnosis, with at least one lesion in the brain with a diameter greater than 5mm on thin-section brain MRI;
- Complete baseline assessment of systemic lesions before treatment, including enhanced brain MRI;
- Informed consent from the patient.
Who cannot join
- Multiple primary or metastatic tumors (except early skin cancer, cervical carcinoma in situ that has been treated radically, with no recurrence or progression for more than 5 years);
- 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.;
- Patients judged by the researcher as unsuitable for brain MRI or stereotactic brain radiotherapy;
- EGFR, ALK, or ROS1 gene mutations;
- Active BMs that could not be controlled by symptomatic treatment, such as mannitol and dexamethasone
- Uncontrolled epilepsy, central nervous system disease, or history of mental disorders, judged by the researcher to potentially interfere with the signing of the informed consent form or affect patient compliance;
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- Symptomatic interstitial lung disease or active infection/non-infectious pneumonia;
- Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation;
- Patients with active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable arrhythmia;
- Other uncontrollable diseases or findings from physical examination or clinical experiments judged by the researcher to potentially interfere with the results or increase the risk of treatment complications for the patient;
- Mixed with small cell lung cancer components;
- Pregnant or lactating women;
- Congenital or acquired immunodeficiency diseases including HIV, or history of organ transplantation, allogeneic stem cell transplantation;
- Known HBV, HCV, active pulmonary tuberculosis infection;
- Patients who have received tumor vaccines, or have been vaccinated with other vaccines within 4 weeks before starting treatment (Note: Seasonal influenza vaccines are usually inactivated vaccines and are allowed, while nasal preparations are usually attenuated live vaccines and are not allowed);
- Concurrent use of other immunomodulators, chemotherapy drugs, drugs in other clinical studies, and long-term use of corticosteroid treatment are not eligible for inclusion;
- Patients allergic or contraindicated to PD-1/PD-L1 inhibitors or chemotherapy drugs.
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
Jianjiao Ni, MD, 13761974092, nijianjiao8@sina.com
About this study
Official title: Cranial Radiotherapy Plus PD-1/PD-L1 Inhibitors and Chemotherapy in Patients With Driver-mutation Negative Non-small Cell Lung Cancer With Stable Brain Metastasis (BRILLIANT)
Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy.
Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety.
Read more
Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities.
However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. We will stratify eligible patients based on the status of BMs (active BM vs stable BM) .
- Conditions
- NSCLC Stage IV, Brain Metastases
- Being tested
- PD-L1/PD-1 inhibitor and chemotherapy, SRT or WBRT
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-L1/PD-1 inhibitor and chemotherapyDrug
Stable brain metastases patients in this arm will receive PD-L1/PD-1 inhibitors and chemotherapy.
SRT or WBRTRadiation
Stable brain metastases (BM) patients in this arm will receive stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) according to their BM condition.
| Study group | Role | What they receive |
|---|---|---|
| stable BM, PD-1/PD-L1 inhibitors plus chemotherapy | Active comparator | Not described Receives: Drug: PD-L1/PD-1 inhibitor and chemotherapy |
| stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy | Experimental | Not described Receives: Drug: PD-L1/PD-1 inhibitor and chemotherapy; Radiation: SRT or WBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) after treatment, assessed according to the RECIST 1.1 criteria.
Measured: 2 years
Secondary outcomes (5)
Intracranial Progression-Free Survival (iPFS)
The time from the start of treatment when the patient is enrolled until the observation of intracranial disease progression (appearance of new lesions, enlargement of existing lesions, excluding the possibility of pseudo-progression such as radiation necrosis) or death from any cause. Patients who have not progressed at the time of analysis will have their last contact date used as the cutoff date.
Measured: 2 years
Intracranial Objective Response Rate (iORR)
The percentage of participants in the analysis population whose brain lesions achieve CR or PR, assessed according to the modified RECIST 1.1 criteria.
Measured: 2 years
Progression-Free Survival (PFS)
The time from the start of treatment until the observation of disease progression or death from any cause, assessed according to the RECIST 1.1 criteria. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.
Measured: 2 years
Overall Survival (OS)
The time from the start of treatment until death from any cause. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.
Measured: 2 years
Treatment-Related Adverse Event (TRAE)
Adverse events related to treatment, as assessed by the researcher, are recorded and evaluated according to the CTCAE version 5.0.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2024
- Study start1 Jul 2024
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC Stage IVStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 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
- NCT06501391
- Sponsor's protocol ID
- 2024Lung-PD1-stable BM
- Status last verified
- Aug 2024
- First submitted
- 9 Jul 2024
- Last updated
- 28 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cranial Radiotherapy Plus PD-1/PD-L1 Inhibitors and Chemotherapy in Patients With Driver-mutation Negative Non-small Cell Lung Cancer With Stable Brain Metastasis (BRILLIANT)
- ClinicalTrials.gov ID
- NCT06501391
- Acronym / sponsor ID
- 2024Lung-PD1-stable BM
- Conditions
- NSCLC Stage IV, Brain Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Jul 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 15 Jul 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.
Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy.
Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety.
Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities.
However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. We will stratify eligible patients based on the status of BMs (active BM vs stable BM) .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| stable BM, PD-1/PD-L1 inhibitors plus chemotherapy | Active comparator | Drug: PD-L1/PD-1 inhibitor and chemotherapy |
| stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy | Experimental | Drug: PD-L1/PD-1 inhibitor and chemotherapy, Radiation: SRT or WBRT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years;
- KPS score ≥ 70;
- Negative genetic testing for common driver genes including EGFR, ALK, ROS-1;
- Pathologically confirmed non-small cell lung cancer;
- Clinical stage IV (AJCC, 8th edition, 2017);
Key exclusion criteria (17 listed)
- Multiple primary or metastatic tumors (except early skin cancer, cervical carcinoma in situ that has been treated radically, with no recurrence or progression for more than 5 years);
- 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.;
- Patients judged by the researcher as unsuitable for brain MRI or stereotactic brain radiotherapy;
- EGFR, ALK, or ROS1 gene mutations;
- Active BMs that could not be controlled by symptomatic treatment, such as mannitol and dexamethasone
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 |
|---|---|---|
| PD-L1/PD-1 inhibitor and chemotherapyStable brain metastases patients in this arm will receive PD-L1/PD-1 inhibitors and chemotherapy. | Drug | stable BM, PD-1/PD-L1 inhibitors plus chemotherapy, stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy |
| SRT or WBRTStable brain metastases (BM) patients in this arm will receive stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) according to their BM condition. | Radiation | stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy |
Primary outcome
Objective Response Rate (ORR)
Time frame: 2 years
The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) after treatment, assessed according to the RECIST 1.1 criteria.
5 secondary outcomes
Intracranial Progression-Free Survival (iPFS)
Time frame: 2 years
Intracranial Objective Response Rate (iORR)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Treatment-Related Adverse Event (TRAE)
Time frame: 2 years
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 28 Aug 2024.
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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 2 study testing PD-L1/PD-1 inhibitor and chemotherapy and SRT or WBRT in people with NSCLC Stage IV 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 8 inclusion and 17 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 28 Aug 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 phase mean?
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 2 years). 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 28 Aug 2024.