Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable Brain Metastasis
NCT Number: NCT06501391
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: NSCLC Stage IV|Brain Metastases
Interventions: DRUG: PD-L1/PD-1 inhibitor and chemotherapy|RADIATION: SRT or WBRT
Sponsor: Fudan University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 54
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-01
Completion Date: 2027-07
Locations: Fudan University Shanghai Cancer Center, Shanghai, China

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. We will stratify eligible patients based on the status of BMs (active BM vs stable BM) .

Primary Outcome Measures: 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., 2 years
Secondary Outcome Measures: 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., 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., 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., 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., 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., 2 years