Cranial Radiotherapy Plus PD-1/PD-L1 Inhibitors and Chemotherapy in Untreated Driver-mutation Negative Non-small Cell Lung Cancer With Active Brain Metastasis (BRILLIANT-1)

Status: Recruiting
Location: See location...
Intervention Type: Radiation, Drug
Study Type: Interventional
Study Phase: Phase 2
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. 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. Though most of the current studies excluded patients with active BM, we believe that these patients need more attention. In this trial, we focus on patients with active BM and treat them with PD-1/PD-L1 inhibitor, chemotherapy and SRT/WBRT.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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;

• Active BMs that could not be controlled by symptomatic treatment, such as mannitol and dexamethasone

• Complete baseline assessment of systemic lesions before treatment, including enhanced brain MRI;

• Informed consent from the patient.

Locations
Other Locations
China
Fudan University Shanghai Cancer Center
RECRUITING
Shanghai
Time Frame
Start Date: 2024-07-01
Estimated Completion Date: 2025-07
Participants
Target number of participants: 40
Treatments
Experimental: active BM
Sponsors
Leads: Fudan University

This content was sourced from clinicaltrials.gov

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