Lung CancerNCT03309462
Analysis of Re-biopsy Specimens in Advanced NSCLC With Acquired Resistance of EGFR-TKI Targeted Therapy
A study testing Miseq sequencer in people with Lung Cancer, run by Shanghai Chest Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Miseq sequencer
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2017to 31 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- EGFR mutations were confirmed by molecular pathology.
- Patients who were treated by the first and the second generation EGFR-TKI.
- Patients were evaluated PD according to RECIST imaging standard.
- Patients with functional status score (Performance Status, PS) for 0-2 points according to the Eastern Cooperative Oncology Group (ECOG) .
- 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.
Who cannot join
- Patients received blood transfusion within 1 month.
- Patients suffering from autoimmune diseases, including but not limited to systemic lupus erythematosus, class of wet arthritis, Sjogren's syndrome.
- Patients with severe disease is not suitable for medical biopsy.
- Patients refused to participate in clinical trials.
- Researchers consider that the patient is not suitable for participating in this clinical trial.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Lung Cancer
- Being tested
- Miseq sequencer
- Keywords
- Next generation sequencing, Re-biopsy, Acquired resistance, Tissue sample, Peripheral blood
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Miseq sequencerDevice
The sequencer will be used to detect the gene mutations of the re-biopsy tissue samples and peripheral blood samples obtained from patients.
| Study group | Role | What they receive |
|---|---|---|
| Re-biopsy tissue sample | Experimental | The gene testing of re-biopsy tissue sample diagnosed with NSCLC will be performed with NGS using Illumina Miseq squencer and Cobas. Receives: Device: Miseq sequencer |
| Peripheral blood sample | Experimental | The peripheral blood sample will be extracted with DNA and performed with NGS using Illumina Miseq squencer and ddPCR. Receives: Device: Miseq sequencer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start1 Sep 2017
- Primary completion30 Jun 2018
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Chest HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Chest Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiayuan Sun, Shanghai Chest Hospital
- Investigators
- Jiayuan Sun, MD, PhD, Principal investigator, Shanghai Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03309462
- Sponsor's protocol ID
- SHCHE201701
- Status last verified
- Dec 2019
- First submitted
- 10 Oct 2017
- Last updated
- 9 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 34173341
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03309462
- Acronym / sponsor ID
- SHCHE201701
- Conditions
- Lung Cancer
- Keywords
- Next generation sequencing, Re-biopsy, Acquired resistance, Tissue sample, Peripheral blood
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Shanghai Chest HospitalUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 13 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Re-biopsy tissue sample | Experimental | Device: Miseq sequencerThe gene testing of re-biopsy tissue sample diagnosed with NSCLC will be performed with NGS using Illumina Miseq squencer and Cobas. |
| Peripheral blood sample | Experimental | Device: Miseq sequencerThe peripheral blood sample will be extracted with DNA and performed with NGS using Illumina Miseq squencer and ddPCR. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- EGFR mutations were confirmed by molecular pathology.
- Patients who were treated by the first and the second generation EGFR-TKI.
- Patients were evaluated PD according to RECIST imaging standard.
- Patients with functional status score (Performance Status, PS) for 0-2 points according to the Eastern Cooperative Oncology Group (ECOG) .
- 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.
Key exclusion criteria (5 listed)
- Patients received blood transfusion within 1 month.
- Patients suffering from autoimmune diseases, including but not limited to systemic lupus erythematosus, class of wet arthritis, Sjogren's syndrome.
- Patients with severe disease is not suitable for medical biopsy.
- Patients refused to participate in clinical trials.
- Researchers consider that the patient is not suitable for participating in this clinical trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Miseq sequencerThe sequencer will be used to detect the gene mutations of the re-biopsy tissue samples and peripheral blood samples obtained from patients. | Device | Peripheral blood sample, Re-biopsy tissue sample |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Derived from this study: PubMed 34173341Zhang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiayuan Sun, MD, PhD principal investigator
Shanghai Chest Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Miseq sequencer in people with Lung Cancer, run by Shanghai Chest Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare the differences of gene mutation between tissue sample and peripheral blood sample by NGS (time frame: up to one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03309462, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.