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

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ClinicalTrials.gov Identifier: NCT03309462
Recruitment Status : Active, not recruiting
First Posted : October 13, 2017
Last Update Posted : December 2, 2017
Sponsor:
Information provided by (Responsible Party):
Jiayuan Sun, Shanghai Chest Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lung Cancer Device: Miseq sequencer Not Applicable

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  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: 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
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : June 30, 2018
Estimated Study Completion Date : July 31, 2018

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Compare the differences of gene mutation between tissue sample and peripheral blood sample by NGS [ Time Frame: up to one year ]
    differences of gene mutation between re-biopsy tissue sample and peripheral blood sample will be tested by NGS



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03309462


Locations
China, Shanghai
Shanghai Chest Hospital
Shanghai, Shanghai, China, 200030
Sponsors and Collaborators
Shanghai Chest Hospital
Investigators
Principal Investigator: Jiayuan Sun, MD, PhD Shanghai Chest Hospital

Responsible Party: Jiayuan Sun, Director, Endoscope Department, Shanghai Chest Hospital, Shanghai Chest Hospital
ClinicalTrials.gov Identifier: NCT03309462     History of Changes
Other Study ID Numbers: SHCHE201701
First Posted: October 13, 2017    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jiayuan Sun, Shanghai Chest Hospital:
Next generation sequencing
Re-biopsy
Acquired resistance
Tissue sample
Peripheral blood

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases