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

Stereotactic Radiotherapy for Non-small Cell Lung Cancer With Oligo-residual Intracranial Disease After First-line Third-generation EGFR Inhibitors: a Multicenter, Randomized Clinical Trial.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer; Brain Metastases
• Intervention / Treatment: Drug: EGFR-TK Inhibitor; Radiation: Stereotactic radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3rd generation EGFR-TKI+SRS; 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.	Drug: EGFR-TK Inhibitor; Patients will receive EGFR-TKI until confirmed progression or unacceptable toxicity.; Radiation: Stereotactic radiotherapy; Patients with oligo-residual intracranial disease after treatment with EGFR-TKI will be treated with SRS of all intracranial lesions. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist.
Active Comparator: 3rd generation EGFR-TKI; The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.	Drug: EGFR-TK Inhibitor; Patients will receive EGFR-TKI until confirmed progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS was measured from the date of randomization to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.	Two years
Health-related quality of life per QLQ-C30	Health-related quality of life was evaluated using the QLQ-C30 questionnaires to assess health-related quality of life.	Two years
Health-related quality of life per QLQ-LC13	Health-related quality of life was evaluated using the QLQ-LC13 questionnaires to assess health-related quality of life.	Two years
Overall Survival	OS was defined as the time from the date of randomization until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.	Three years
Intracranial progression-free survival	iPFS was defined as the time from the start of randomization 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.	Two years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Qian Chu, Tongji Hospital; Principal Investigator: Zhengfei Zhu, MD, Fudan University; Principal Investigator: Xuwei Cai, Shanghai Chest Hospital; Principal Investigator: Lin Wu, Hunan Cancer Hospital; Principal Investigator: Rongrong Zhou, Xiangya Hospital of Central South University; Principal Investigator: Guang Han, Hubei Cancer Hospital; Principal Investigator: Hui Zhu, Shandong Cancer Hospital And Institute; Principal Investigator: Jinjun Ye, Jiangsu Cancer Institute & Hospital; Principal Investigator: Xiaojia Cui, The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China; Principal Investigator: Guomei Tai, The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China; Principal Investigator: Zhiyong Yuan, Tianjin Medical University Cancer Institute and Hospital; Principal Investigator: Dejun XIng, Jilin Provincial Tumor Hospital; Principal Investigator: Jichen Ren, Jilin Provincial Tumor Hospital; Principal Investigator: Yanyang Wang, General Hospital of Ningxia Medical University; Principal Investigator: Chuangzhou Rao, Ningbo No.2 Hospital; Principal Investigator: Bing Lu, The Affiliated Hospital of Guizhou Medical University; Principal Investigator: Zhongyi Dong, Nanfang Hospital, Southern Medical University; Principal Investigator: Jiwei Liu, The First Affiliated Hospital of Dalian Medical University; Principal Investigator: Zhenzhou Yang, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Hongqing Zhuang, Peking University Third Hospital; Principal Investigator: Anwen Liu, Nanchang University Second Affiliated Hospital; Principal Investigator: Haihua Yang, Taizhou Hospital Affiliated to Wenzhou Medical University; Principal Investigator: Fang Liu, Chinese PLA General Hospital; Principal Investigator: Yong Mao, Affiliated Hospital of Jiangnan University; Principal Investigator: Xiaorong Dong, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Principal Investigator: Jiancheng Li, Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): August 10, 2028

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 27, 2023
• First Posted (Actual): August 31, 2023

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 2306276-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No