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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03309462
Recruitment Status : Completed
First Posted : October 13, 2017
Last Update Posted : December 9, 2019
Sponsor:
Information provided by (Responsible Party):
Jiayuan Sun, Shanghai Chest Hospital

Tracking Information
First Submitted Date  ICMJE October 10, 2017
First Posted Date  ICMJE October 13, 2017
Last Update Posted Date December 9, 2019
Actual Study Start Date  ICMJE September 1, 2017
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 10, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Analysis of Re-biopsy Specimens in Advanced NSCLC With Acquired Resistance of EGFR-TKI Targeted Therapy
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Lung Cancer
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.
    Intervention: Device: Miseq sequencer
  • Experimental: Peripheral blood sample
    The peripheral blood sample will be extracted with DNA and performed with NGS using Illumina Miseq squencer and ddPCR.
    Intervention: Device: Miseq sequencer
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2017)
50
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 31, 2019
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03309462
Other Study ID Numbers  ICMJE SHCHE201701
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jiayuan Sun, Shanghai Chest Hospital
Study Sponsor  ICMJE Shanghai Chest Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jiayuan Sun, MD, PhD Shanghai Chest Hospital
PRS Account Shanghai Chest Hospital
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP