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

NCT06020066 | Active Not Recruiting Phase 2

• 1 other identifier: 2306276-14
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall Survival

  Three years

• Intracranial progression-free survival

  Two years

• Health-related quality of life per QLQ-C30

  Two years

• Health-related quality of life per QLQ-LC13

  Two years

• Percentage of Participants With Adverse Events

  Two years

Study Arms (2)

3rd generation EGFR-TKI+SRS

EXPERIMENTAL

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; Radiation: Stereotactic radiotherapy

3rd generation EGFR-TKI

ACTIVE COMPARATOR

The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.

Drug: EGFR-TK Inhibitor

Interventions

EGFR-TK Inhibitor DRUG

Patients will receive EGFR-TKI until confirmed progression or unacceptable toxicity.

3rd generation EGFR-TKI; 3rd generation EGFR-TKI+SRS

Stereotactic radiotherapy RADIATION

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.

3rd generation EGFR-TKI+SRS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200030, China

Location

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zhengfei Zhu, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

• Xuwei Cai

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

• Qian Chu

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

• Xiaorong Dong

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  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

• Jiancheng Li

  Fujian Cancer 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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 31, 2023
• Study Start: August 10, 2023
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): August 10, 2028
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)