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NCT Number: NCT05598528

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

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.

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Key information

Conditions

Lung Cancer, Non-small Cell Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Circulating Tumor DNA EGFR Gene Mutation EGFR-TKI Resistant Mutation Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Primary Resistance Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Oncology, The Second Xiangya Hospital, Central South University

Changsha, Hunan, 410011, China

Location status: Recruiting

Location contact

Fang Wu, MD, PhD

CONTACT

[email protected]

+86 13574858332

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age >18 years;
  • Histological or cytopathological diagnosed NSCLC;
  • 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;
  • At least one measurable lesion can be evaluated according to the Response Evaluation Criteria In Solid Tumours v1.1 (RECIST1.1) criteria;
  • Positive EGFR mutation confirmed by tissue or cytology (pleural fluid, cerebrospinal fluid, etc.);
  • Use of third-generation EGFR-TKIs approved by the NMPA for NSCLC as first-line therapy;
  • 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;
  • Agree to participate in this study and sign an informed consent form.

Exclusion criteria

  • Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form;
  • Pregnant and lactating women;
  • Other malignant neoplastic diseases within 3 years;
  • Patients who have undergone other clinical drug trials;
  • Received systemic anti-tumor therapy within 2 years;

Treatment and study plan

Genomic profiles detection

Other

The Paraffin-embedded tumor tissue at diagnosis is collected and assessed by Next- generation gene sequencing

circulating tumor DNA detection

Other

The Plasma at diagnosis and at 1-month treatment are collected and assessed by Next-generation gene sequencing

Primary outcomes

  1. Objective Response Rate (ORR)

    Time frame: 2 years

    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. Progression-free survival (PFS)

    Time frame: 3 years

    Time from the beginning of treatment to the first disease progression (PD) in patients with advanced NSCLC

  3. Differences in genomic profiles of tumor tissues and ctDNA clearance of third-generation EGFR-TKIs sensitive and primary drug-resistant NSCLC.

    Time frame: 3 years

    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.

Secondary outcomes

  1. Overall survival (OS)

    Time frame: 5 years

    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

  2. Disease Control Rate (DCR)

    Time frame: 3 years

    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)

Other outcomes

  1. The correlation between tumor microenvironment signature and efficacy of 3rd EGFR-TKIs

    Time frame: 3 years

    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.

Sponsors and collaborators

Lead sponsor

Second Xiangya Hospital of Central South University

Other

Collaborators

  • 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 Traditional 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 City
  • 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
  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • University of South China Affiliated Nanhua Hospital
  • West China Hospital
  • 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

Registry information

Official study 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)

Acronym: PRECISE

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Oct 28, 2022
Registry last updated
Dec 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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