Analysis of Re-biopsy Specimens in Advanced NSCLC With Acquired Resistance of EGFR-TKI Targeted Therapy

Analysis of Re-biopsy Specimens in Advanced Non-small Cell Lung Cancer With Acquired Resistance of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Targeted Therapy

The objective of the study is to reveal the acquired resistance mechanism of the first and second generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) in tissue and plasma using Next Generation Sequencing (NGS) and the difference of ctDNA in plasma and DNA in biopsy samples is compared and the consistency of two samples was observed. At the same time, the sensitivity, specificity and the consistency of detecting T790M mutation using ddPCR, Cobas and NGS were compared.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Device: Miseq sequencer

Detailed Description

With the deepening of the concept of tumor management, it is necessary to monitor the patient's gene during the course of treatment, especially in patients with acquired resistance of the first generation EGFR-TKI. Re-biopsy can effectively provide tissue samples as a "gold standard" for gene detection samples. While, the plasma circulating tumor DNA (ctDNA) detection is an important sample of gene detection and the treatment when tissue samples cannot be assessed. However, due to tumor heterogeneity and ctDNA detection technique sensitivity, plasma ctDNA and tissue samples of the test results are inconsistent. Therefore, the difference between re-biopsy tissue samples and plasma ctDNA samples will provide strong evidence for the application of plasma ctDNA in TKI-resistant patients.

The study was designed as a prospective and single center study. Fifty patients will be enrolled into the study and the clinical data of patients, including smoke history, cancer history, location, pathology, gene mutation status and so on of the first biopsy samples will be collected and recorded in a case report form. For patients recruited in the study, lesions which were assessed as progressive disease(PD) will be obtained by interventional pulmonology technology. And about 20ml peripheral blood will be collected at the same time. The tissue will be divided into two parts, one part was sent to Pathology Department of Shanghai Chest Hospital and will be processed with paraffin-embedded, and for those diagnosed NSCLC, the other part will be extracted with DNA and performed NGS for the qualified DNA sample and using Cobas to detect the T790M mutation. The matched peripheral blood will also be extracted with DNA and performed NGS and ddPCR.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. EGFR mutations were confirmed by molecular pathology.
2. Patients who were treated by the first and the second generation EGFR-TKI.
3. Patients were evaluated PD according to RECIST imaging standard.
4. Patients with functional status score (Performance Status, PS) for 0-2 points according to the Eastern Cooperative Oncology Group (ECOG) .
5. Patients can receive histological / cytological specimens through microsurgical biopsy techniques, including but not limited to transbronchial biopsy (TBB), transbronchial lung biopsy (TBLB), transabonchial needle aspiration (TBNA), CT / ultrasound guided thoracic needle aspiration biopsy (CT / ultrasound guided-TTNA), ultrasound-guided superficial lymph node biopsy.

Exclusion Criteria:

1. Patients received blood transfusion within 1 month.
2. Patients suffering from autoimmune diseases, including but not limited to systemic lupus erythematosus, class of wet arthritis, Sjogren's syndrome.
3. Patients with severe disease is not suitable for medical biopsy.
4. Patients refused to participate in clinical trials.
5. Researchers consider that the patient is not suitable for participating in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Re-biopsy tissue sample; The gene testing of re-biopsy tissue sample diagnosed with NSCLC will be performed with NGS using Illumina Miseq squencer and Cobas.	Device: Miseq sequencer; The sequencer will be used to detect the gene mutations of the re-biopsy tissue samples and peripheral blood samples obtained from patients.
Experimental: Peripheral blood sample; The peripheral blood sample will be extracted with DNA and performed with NGS using Illumina Miseq squencer and ddPCR.	Device: Miseq sequencer; The sequencer will be used to detect the gene mutations of the re-biopsy tissue samples and peripheral blood samples obtained from patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the differences of gene mutation between tissue sample and peripheral blood sample by NGS	differences of gene mutation between re-biopsy tissue sample and peripheral blood sample will be tested by NGS	up to one year

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Investigators: Principal Investigator: Jiayuan Sun, MD, PHD, Shanghai Chest Hospital

Publications and helpful links

General Publications

• Zhang Y, Xiong L, Xie F, Zheng X, Li Y, Zhu L, Sun J. Next-generation sequencing of tissue and circulating tumor DNA: Resistance mechanisms to EGFR targeted therapy in a cohort of patients with advanced non-small cell lung cancer. Cancer Med. 2021 Jul;10(14):4697-4709. doi: 10.1002/cam4.3948. Epub 2021 Jun 25.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 9, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Next generation sequencing; Peripheral blood; Re-biopsy; Acquired resistance; Tissue sample
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: SHCHE201701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No