Back to resultsSRS for NSCLC With Oligo-residual Intracranial Disease After First-line 3rd Generation EGFR-TKI
Primary Purpose
Brain Metastases, Non-small Cell Lung Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
EGFR-TK Inhibitor
Stereotactic radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Brain Metastases
Eligibility Criteria
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.
Sites / Locations
- Fudan University Shanghai Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
3rd generation EGFR-TKI+SRS
3rd generation EGFR-TKI
Arm Description
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.
The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.
Outcomes
Primary Outcome Measures
Progression-free survival
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
Overall Survival
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
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
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
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
Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06020066
Brief Title
SRS for NSCLC With Oligo-residual Intracranial Disease After First-line 3rd Generation EGFR-TKI
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 10, 2023 (Actual)
Primary Completion Date
August 10, 2028 (Anticipated)
Study Completion Date
August 10, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases, Non-small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
202 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
3rd generation EGFR-TKI+SRS
Arm Type
Experimental
Arm Description
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.
Arm Title
3rd generation EGFR-TKI
Arm Type
Active Comparator
Arm Description
The control group will receive 3rd generation EGFR-TKI until disease progression or intolerable toxicity occurs.
Intervention Type
Drug
Intervention Name(s)
EGFR-TK Inhibitor
Intervention Description
Patients will receive EGFR-TKI until confirmed progression or unacceptable toxicity.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic radiotherapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
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
Time Frame
Two years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
Three years
Title
Intracranial progression-free survival
Description
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.
Time Frame
Two years
Title
Health-related quality of life per QLQ-C30
Description
Health-related quality of life was evaluated using the QLQ-C30 questionnaires to assess health-related quality of life.
Time Frame
Two years
Title
Health-related quality of life per QLQ-LC13
Description
Health-related quality of life was evaluated using the QLQ-LC13 questionnaires to assess health-related quality of life.
Time Frame
Two years
Title
Percentage of Participants With Adverse Events
Description
Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.
Time Frame
Two years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhengfei Zhu
Phone
+8618017312901
Email
fuscczzf@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhengfei Zhu, MD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xuwei Cai
Organizational Affiliation
Shanghai Chest Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Qian Chu
Organizational Affiliation
Tongji Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xiaorong Dong
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lin Wu
Organizational Affiliation
Hunan Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rongrong Zhou
Organizational Affiliation
Xiangya Hospital of Central South University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Guang Han
Organizational Affiliation
Hubei Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hui Zhu
Organizational Affiliation
Shandong Cancer Hospital and Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jinjun Ye
Organizational Affiliation
Jiangsu Cancer Institute & Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xiaojia Cui
Organizational Affiliation
The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Guomei Tai
Organizational Affiliation
The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhiyong Yuan
Organizational Affiliation
Tianjin Medical University Cancer Institute and Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dejun XIng
Organizational Affiliation
Jilin Provincial Tumor Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jichen Ren
Organizational Affiliation
Jilin Provincial Tumor Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jiancheng Li
Organizational Affiliation
Fujian Medical University Cancer Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yanyang Wang
Organizational Affiliation
General Hospital of Ningxia Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Chuangzhou Rao
Organizational Affiliation
Ningbo No.2 Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bing Lu
Organizational Affiliation
The Affiliated Hospital Of Guizhou Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhongyi Dong
Organizational Affiliation
Nanfang Hospital, Southern Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jiwei Liu
Organizational Affiliation
The First Affiliated Hospital of Dalian Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhenzhou Yang
Organizational Affiliation
The Second Affiliated Hospital of Chongqing Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hongqing Zhuang
Organizational Affiliation
Peking University Third Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anwen Liu
Organizational Affiliation
Nanchang University Second Affiliated Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Haihua Yang
Organizational Affiliation
Taizhou Hospital Affiliated to Wenzhou Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fang Liu
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yong Mao
Organizational Affiliation
Affiliated Hospital of Jiangnan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhengfei Zhu, MD
Phone
+8618017312901
Email
fuscczzf@163.com
First Name & Middle Initial & Last Name & Degree
Jianjiao Ni, MD
Email
nijianjiao8@sina.com
12. IPD Sharing Statement
Learn more about this trial
SRS for NSCLC With Oligo-residual Intracranial Disease After First-line 3rd Generation EGFR-TKI
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