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

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ClinicalTrials.gov Identifier: NCT05598528
Recruitment Status : Recruiting
First Posted : October 28, 2022
Last Update Posted : October 28, 2022
Sponsor:
Collaborators:
Xiangya Hospital of Central South University
Shanghai Chest Hospital
West China Hospital
Hunan Cancer Hospital
The Third Xiangya Hospital of Central South University
The First Affiliated Hospital of Xiamen University
Second Affiliated Hospital, School of Medicine, Zhejiang University
China-Japan Friendship Hospital
Fudan University
Jiangxi Provincial Cancer Hospital
The First Affiliated Hospital of Kunming Medical College
Loudi Central Hospital
ZhuZhou Central Hospital
Xiangtan Central Hospital
First People's Hospital of Chenzhou
Yueyang Central Hospital
Yongzhou Central Hospital
The First Affiliated Hospital of University of South China
Hunan Provincial People's Hospital
Shaoyang Central Hospital
Yiyang Central Hospital
Changsha Central Hospital
The first people's hospital of Guiyang
Wuhan Union Hospital, China
Renmin Hospital of Wuhan University
The First People's Hospital of Changde
Zhuzhou Second Hospital
First Hospital of Changsha
Hengyang Central Hospital
Huaihua first people's Hospital
The First People's Hospital of Xiangtan
University of South China Affiliated Nanhua Hospital
Xiangxi Autonomous Prefecture People's Hospital
People's Hospital of Zhangjiajie
Second People's Hospital Of Huaihua
Hunan Academy of Traditional Chinese Medicine Affiliated Hospital
The Third Hospital of Changsha
Xiangya Changde Hospital
Changsha County first People's Hospital
Hunan Provincial Straight Hospital of Traditional Chinese Medicine
Liuyang Hospital of traditional Chinese Medicine
Information provided by (Responsible Party):
Fang Wu, Second Xiangya Hospital of Central South University

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.


Condition or disease Intervention/treatment
Lung Cancer, Non-small Cell EGFR Gene Mutation EGFR-TKI Resistant Mutation Primary Resistance Circulating Tumor DNA Other: Genomic profiles detection Other: circulating tumor DNA detection

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 210 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
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)
Actual Study Start Date : September 28, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
EGFR-positive lung patients recieving 3rd generation EGFR-TKIs as first-line therapy
Stage III-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.
Other: Genomic profiles detection
The Paraffin-embedded tumor tissue at diagnosis is collected and assessed by Next- generation gene sequencing

Other: circulating tumor DNA detection
The Plasma at diagnosis and at 1-month treatment are collected and assessed by Next-generation gene sequencing




Primary Outcome Measures :
  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 first-line immunotherapy to the first 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 ORR 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 Outcome Measures :
  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 Outcome Measures:
  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.


Biospecimen Retention:   Samples With DNA
  1. The paraffin embeds tumor tissue at diognosis
  2. Peripheral venous blood


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Stage III-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.
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05598528


Locations
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China, Hunan
Department of Oncology, The Second Xiangya Hospital, Central South University Recruiting
Changsha, Hunan, China, 410011
Contact: Fang Wu, MD, PhD    +86 13574858332    wufang4461@csu.edu.cn   
Sponsors and Collaborators
Fang Wu
Xiangya Hospital of Central South University
Shanghai Chest Hospital
West China Hospital
Hunan Cancer Hospital
The Third Xiangya Hospital of Central South University
The First Affiliated Hospital of Xiamen University
Second Affiliated Hospital, School of Medicine, Zhejiang University
China-Japan Friendship Hospital
Fudan University
Jiangxi Provincial Cancer Hospital
The First Affiliated Hospital of Kunming Medical College
Loudi Central Hospital
ZhuZhou Central Hospital
Xiangtan Central Hospital
First People's Hospital of Chenzhou
Yueyang Central Hospital
Yongzhou Central Hospital
The First Affiliated Hospital of University of South China
Hunan Provincial People's Hospital
Shaoyang Central Hospital
Yiyang Central Hospital
Changsha Central Hospital
The first people's hospital of Guiyang
Wuhan Union Hospital, China
Renmin Hospital of Wuhan University
The First People's Hospital of Changde
Zhuzhou Second Hospital
First Hospital of Changsha
Hengyang Central Hospital
Huaihua first people's Hospital
The First People's Hospital of Xiangtan
University of South China Affiliated Nanhua Hospital
Xiangxi Autonomous Prefecture People's Hospital
People's Hospital of Zhangjiajie
Second People's Hospital Of Huaihua
Hunan Academy of Traditional Chinese Medicine Affiliated Hospital
The Third Hospital of Changsha
Xiangya Changde Hospital
Changsha County first People's Hospital
Hunan Provincial Straight Hospital of Traditional Chinese Medicine
Liuyang Hospital of traditional Chinese Medicine
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Responsible Party: Fang Wu, Associate Professor, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT05598528    
Other Study ID Numbers: XYEYY20220928
First Posted: October 28, 2022    Key Record Dates
Last Update Posted: October 28, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases