Clinical trial NCT05598528: Exploring the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Cancer, Non-small Cell
EGFR Gene Mutation
EGFR-TKI Resistant Mutation
Primary Resistance
Circulating Tumor DNA
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Xiangya Hospital of Central South University
name: Shanghai Chest Hospital
name: West China Hospital
name: Hunan Cancer Hospital
name: The Third Xiangya Hospital of Central South University
name: The First Affiliated Hospital of Xiamen University
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: China-Japan Friendship Hospital
name: Fudan University
name: First Affiliated Hospital of Kunming Medical University
name: Loudi Central Hospital
name: ZhuZhou Central Hospital
name: Xiangtan Central Hospital
name: First People's Hospital of Chenzhou
name: Yueyang Central Hospital
name: Yongzhou Central Hospital
name: The First Affiliated Hospital of University of South China
name: Hunan Provincial People's Hospital
name: Shaoyang Central Hospital
name: Yiyang Central Hospital
name: Changsha Central Hospital
name: The first people's hospital of Guiyang
name: Wuhan Union Hospital, China
name: Renmin Hospital of Wuhan University
name: The First People's Hospital of Changde City
name: Zhuzhou Second Hospital
name: First Hospital of Changsha
name: Hengyang Central Hospital
name: Huaihua first people's Hospital
name: The First People's Hospital of Xiangtan
name: University of South China Affiliated Nanhua Hospital
name: Xiangxi Autonomous Prefecture People's Hospital
name: People's Hospital of Zhangjiajie
name: Second People's Hospital Of Huaihua
name: Hunan Academy of Traditional Chinese Medicine Affiliated Hospital
name: The Third Hospital of Changsha
name: Xiangya Changde Hospital
name: Changsha County first People's Hospital
name: Hunan Provincial Straight Hospital of Traditional Chinese Medicine
name: Liuyang Hospital of traditional Chinese Medicine
name: Second People's Hospital of Hunan
name: First Affiliated Hospital of Guangxi Medical University
name: Guiyang Public Health Treatment Center
name: The Affiliated Bethune Hospital of Shanxi Medical University
name: Hunan University of Traditional Chinese Medicine
name: Tongji Hospital
name: The First Affiliated Hospital of Nanchang University
First posted: 2022-10-28
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stage IIIB-IV EGFR-positive lung patients receiving 3rd generation EGFR-TKIs (Osimertinib 80mg/Qd or Almonertinib 110mg/Qd or Furmonertinib 80mg/Qd) as first-line therapy.

Brief 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.


Eligibility criteria: 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;

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 3 years
measure: Differences in genomic profiles of tumor tissues and ctDNA clearance of third-generation EGFR-TKIs sensitive and primary drug-resistant NSCLC.
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years
measure: Disease Control Rate (DCR)
timeFrame: 3 years
Other outcomes:
measure: The correlation between tumor microenvironment signature and efficacy of 3rd EGFR-TKIs
timeFrame: 3 years
Locations:
city: Changsha
country: China
facility: Department of Oncology, The Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
References: