Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable Brain Metastasis

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)

Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable Brain Metastasis (NCT06501391) is a Phase 2 interventional studying NSCLC Stage IV and Brain Metastases, sponsored by Fudan University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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) .

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against NSCLC Stage IV and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 54 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused NSCLC Stage IV subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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; - willing to sign a consent form from the patient. Who Should NOT Join This Trial: - 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 conditions (where your immune system attacks your own body)s: 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 willing to sign a consent form form or affect patient compliance; - 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; ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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. Exclusion Criteria: * 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; * 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.

Treatments Being Tested

DRUG

PD-L1/PD-1 inhibitor and chemotherapy

Stable brain metastases patients in this arm will receive PD-L1/PD-1 inhibitors and chemotherapy.

RADIATION

SRT or WBRT

Stable brain metastases (BM) patients in this arm will receive stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) according to their BM condition.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Fudan University Shanghai Cancer Center

Shanghai, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06501391), the sponsor (Fudan University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06501391 clinical trial studying?

Who can participate in NCT06501391?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06501391?

Contact information for this trial may be available directly on the ClinicalTrials.gov record. Click "View on ClinicalTrials.gov" in the sidebar for the official source. Always discuss any potential trial with your doctor before contacting the study site.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06501391. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06501391. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.