SRS for NSCLC With Oligo-residual Intracranial Disease After First-line 3rd Generation EGFR-TKI

Phase 2

Recruiting

• Conditions: Brain Metastases; Non-small Cell Lung Cancer
• Interventions: Drug: EGFR-TK Inhibitor; Radiation: Stereotactic radiotherapy

• Registration Number: NCT06020066
• Lead Sponsor: Fudan University

Brief Summary

Despite the impressive response rate to third-generation EGFR-TKIs, resistance inevitably develops in most patients. Stereotactic radiotherapy plays a growing role in the management of patients with brain metastasis. This study aims to evaluate the efficacy and safety of stereotactic radiotherapy for oligo-residual intracranial disease after first-line third-generation EGFR Inhibitors.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-08
• Study Start: 2023-08-10
• Study First Submitted: 2023-08-18
• Study First Submitted QC: 2023-08-27
• Last Update Submitted: 2023-08-27
• Study First Posted: 2023-08-31
• Last Update Posted: 2023-08-31
• Primary Completion: 2028-08-10
• Study Completion: 2029-08-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 202

Inclusion Criteria

• Pathologically confirmed non-small cell lung cancer;

• Clinical stage IV (AJCC, 8th edition, 2017);

• EGFR mutations: EGFR L858R, EGFR exon 19 deletion;

• Age ≥18 years;

• KPS score ≥70;

• Brain metastasis at the time of diagnosis;

• Complete baseline imaging assessment of metastatic lesions, including enhanced MRI for brain;

• Receiving first-line treatment with third-generation EGFR inhibitors;

• After 3-6 months of third-generation EGFR inhibitor treatment, imaging review indicates no progression of extracranial lesions, and brain lesions are evaluated by thin-layer (1mm layer) enhanced MRI, meeting the following criteria:

  • No more than 10 remaining brain lesions;

    • The maximum diameter of the remaining brain lesions does not exceed 3cm;

      • At least one remaining brain lesion has a diameter greater than 5mm;

        • After evaluation by the researcher, all remaining brain lesions are suitable for stereotactic radiotherapy.

• Patient informed consent.

Exclusion Criteria

• Poor compliance with the study protocol in the investigator's opinion;
• Patients withdrew their informed consent and requested to withdraw from the study;
• Patients were unable to receive regular doses of third-generation EGFR inhibitors due to other underlying conditions, viral side effects, economic factors, etc. (e.g., continuous discontinuation for more than 1 week, cumulative discontinuation for more than 2 weeks).
• Patients did not follow the protocol for follow-up visits as required by this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3rd generation EGFR-TKI+SRS	EGFR-TK Inhibitor	The experimental arm will undergo stereotactic radiotherapy targeting all residual lesions in the brain (completed in a single or multiple treatment courses within one month), while continuing EGFR-TKI therapy until disease progression or intolerable toxicity occurs.
3rd generation EGFR-TKI+SRS	Stereotactic radiotherapy	The experimental arm will undergo stereotactic radiotherapy targeting all residual lesions in the brain (completed in a single or multiple treatment courses within one month), while continuing EGFR-TKI therapy until disease progression or intolerable toxicity occurs.
3rd generation EGFR-TKI	EGFR-TK Inhibitor	The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Two years	PFS was measured from the date of the initiation of EGFR-TKI to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Three years	OS was defined as the time from the date of the initiation of EGFR-TKI until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.
Intracranial progression-free survival	Two years	iPFS was defined as the time from the start of third-generation EGFR-TKI treatment to the occurrence of intracranial disease progression or death. If the subject first experiences extracranial disease progression (without concurrent intracranial disease progression), the date of first extracranial disease progression will be used as the cut-off date. For patients who have not progressed at the time of analysis, the date of their last contact will be used as the cut-off date.
Health-related quality of life per QLQ-C30	Two years	Health-related quality of life was evaluated using the QLQ-C30 questionnaires to assess health-related quality of life.
Health-related quality of life per QLQ-LC13	Two years	Health-related quality of life was evaluated using the QLQ-LC13 questionnaires to assess health-related quality of life.
Percentage of Participants With Adverse Events	Two years	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China