Exploring the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)

EGFR Gene Mutation Clinical Trial

— PRECISE  

Official title:

A Multicenter Clinical Study to Explore the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05598528
• Other study ID #: XYEYY20220928
• Status: Recruiting
• Start date: September 28, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Second Xiangya Hospital of Central South University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Lung cancer is currently the world's largest malignant tumor for cancer-related deaths with non-small cell lung cancer (NSCLC) accounting for 80%-85%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially the 3rd-generation EGFR-TKIs have demonstrated strong antitumor effects in EGFR-positive patients.

However, approximately 20% of EGFR-positive were primarily resistant to 3rd generation EGFR-TKIs, i.e., clinical non-response or disease progression in the short term.

This study aimed to clarify the molecular indicators that predict the benefits of 3-rd EGFR-TKIs as first-line therapy in NSCLCpatients with EGFR-positive. Further, to clarify their primary drug resistance mechanisms, which is of great significance for the treatment and clinical decision-making of NSCLC disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >18 years;

2. Histological or cytopathological diagnosed NSCLC;

3. According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is unresectable IIIB-IV or recurrence and metastasis after surgery;

4. At least one measurable lesion can be evaluated according to the Response Evaluation Criteria In Solid Tumours v1.1 (RECIST1.1) criteria;

5. Positive EGFR mutation confirmed by tissue or cytology (pleural fluid, cerebrospinal fluid, etc.);

6. Use of third-generation EGFR-TKIs approved by the NMPA for NSCLC as first-line therapy;

7. Cooperate with the provision of clinicopathological data, imaging data, sample collection, and follow-up required for the research process, and agree to use the test data for subsequent research and product development;

8. Agree to participate in this study and sign an informed consent form.

Exclusion Criteria:

1. Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form;

2. Pregnant and lactating women;

3. Other malignant neoplastic diseases within 3 years;

4. Patients who have undergone other clinical drug trials;

5. Received systemic anti-tumor therapy within 2 years;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Circulating Tumor DNA
• EGFR Gene Mutation
• EGFR-TKI Resistant Mutation
• Lung Cancer, Non-small Cell

Intervention

Other:
• Genomic profiles detection
The Paraffin-embedded tumor tissue at diagnosis is collected and assessed by Next- generation gene sequencing
• circulating tumor DNA detection
The Plasma at diagnosis and at 1-month treatment are collected and assessed by Next-generation gene sequencing

Locations

Country	Name	City	State
China	Department of Oncology, The Second Xiangya Hospital, Central South University	Changsha	Hunan

Sponsors (48)

Lead Sponsor

Collaborator

Second Xiangya Hospital of Central South University

Changsha Central Hospital, Changsha County first People's Hospital, China-Japan Friendship Hospital, First Affiliated Hospital of Guangxi Medical University, First Affiliated Hospital of Kunming Medical University, First Hospital of Changsha, First People's Hospital of Chenzhou, Fudan University, Guiyang Public Health Treatment Center, Hengyang Central Hospital, Huaihua first people's Hospital, Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Hunan Cancer Hospital, Hunan Provincial People's Hospital, Hunan Provincial Straight Hospital of Traditional Chinese Medicine, Liuyang Hospital of traditional Chinese Medicine, Loudi Central Hospital, People's Hospital of Zhangjiajie, Renmin Hospital of Wuhan University, Second Affiliated Hospital, School of Medicine, Zhejiang University, Second People's Hospital Of Huaihua, Second People's Hospital of Hunan, Shanghai Chest Hospital, Shaoyang Central Hospital, The Affiliated Bethune Hospital of Shanxi Medical University, The First Affiliated Hospital of Hunan University of Chinese Medicine, The First Affiliated Hospital of Nanchang University, The First Affiliated Hospital of University of South China, The First Affiliated Hospital of Xiamen University, The First People's Hospital of Changde, The first people's hospital of Guiyang, The First People's Hospital of Xiangtan, The Third Hospital of Changsha, The Third Xiangya Hospital of Central South University, Tongji Hospital, University of South China Affiliated Nanhua Hospital, West China Hospital, Wuhan Union Hospital, China, Xiangtan Central Hospital, Xiangxi Autonomous Prefecture People's Hospital, Xiangya Changde Hospital, Xiangya Hospital of Central South University, Yiyang Central Hospital, Yongzhou Central Hospital, Yueyang Central Hospital, ZhuZhou Central Hospital, Zhuzhou Second Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The correlation between tumor microenvironment signature and efficacy of 3rd EGFR-TKIs	The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between tumor microenvironment signature and primary resistance and the efficacy of 3rd EGFR-TKIs during the enrolled observation process.	3 years
Primary	Objective Response Rate (ORR)	The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	2 years
Primary	Progression-free survival (PFS)	Time from the beginning of treatment to the first disease progression (PD) in patients with advanced NSCLC	3 years
Primary	Differences in genomic profiles of tumor tissues and ctDNA clearance of third-generation EGFR-TKIs sensitive and primary drug-resistant NSCLC.	The patients who don't achieve partial response or progress within 6 months are defined as the primary resistant group. The genomic profiles and ctDNA clearance detected by Next-generation gene sequencing will be compared between the primary drug-resistant group and sensitive-drug group.	3 years
Secondary	Overall survival (OS)	Overall survival (OS) is defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status	5 years
Secondary	Disease Control Rate (DCR)	The proportion of patients with a complete response or partial response or stable desease to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	3 years