Non Small Cell Lung CancerNCT03771404
NSCLC Heterogeneity in Early Stage Patients and Prediction of Relapse Using a Personalized "Liquid Biopsy"
A study testing blood sampling in people with Non Small Cell Lung Cancer, run by Hellenic Oncology Research Group at 6 sites in Greece.
Trial summary
The purpose of his study is to investigate the intra tumor heterogeneity of the primary tumor and the involved lymph nodes from patients with resectable NSCLC, to detect primary tumor genetic alternations using "liquid biopsy" during the patients' clinical follow up and to correlate the "liquid biopsy" information… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 6 sitesGreece
- Study dates
- 5 Jan 2018to 1 Dec 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed NSCLC (adenocarcinoma and squamous cell carcinoma).
- Age ≥ 18 years
- Operable (stages I-IIIA) NSCLC
- Patients with signed written informed consent obtained according to local guidelines
Who cannot join
- Patients < 18 years
- Patients with non operable NSCLC (regardless of disease stage)
- Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Greece6 sites, 6 recruiting
- Recruiting
2nd Pneumological Dept, GNA "Sotiria"
Athens, Attica, 11527
Aggeliki Rapti, MD
Aggeliki Rapti, MD
- Recruiting
7th Pneumological Dept, GNA "Sotiria"
Athens, Attica, 11527
Mina Gaga, MD
Mina Gaga, MD
- Recruiting
Thoracic Surgery Dept, GNA "Sotiria"
Athens, Attica, 11527
Evaggelos Sepsas, MD
Evaggelos Sepsas, MD
- Not yet recruiting
Thoracic Surgery Clinic, "Hygeia" Hospital
Athens, Attica, 15123
Kosmas Iliadis, MD
Kosmas Iliadis, MD
- Recruiting
Oncology Unit, 3rd Department of Medicine Athens University School of Medicine Athens, GNA "Sotiria"
Athens, 11527
Konstantinos Syrigos, MD,PhD,FCCP
Konstantinos Syrigos, MD,PhD,FCCP
- Recruiting
IASO General Hospital
Athens
Vassilis Georgoulias, MD, PhD, +302106502639
Vassilis Georgoulias, MD, PhD
About this study
Official title: Evaluation of Non-small Cell Lung Carcinoma Genetic Heterogeneity in Patients With Operable Early Stage Disease and Prediction of Clinical Relapse Using a Personalized "Liquid Biopsy"
The purpose of his study is to investigate the intra tumor heterogeneity of the primary tumor and the involved lymph nodes from patients with resectable NSCLC, to detect primary tumor genetic alternations using "liquid biopsy" during the patients' clinical follow up and to correlate the "liquid biopsy" information with the disease recurrence.
Read the detailed description
Lung cancer is the most common cancer in the world. In operable early stage patients NSCLS can be curable, but even after complete primary tumor resection, about 45% of early stage patients develop local or distant recurrence within 8-18 months. Recent studies have established that targeted therapies may fail to cure the disease because of tumor heterogeneity. The presence of genetic heterogeneity in different portions of a tumor have demonstrated its importance in tumor biology suggesting that pre-existing genetically different sub clones may be selected by therapy or differentially involved in the metastatic process, leading to treatment failure.
The relationship of tumor heterogeneity with the poor clinical outcome suggests that its assessment could provide interesting and useful clinical information, especially, in terms of prognosis and treatment selection. It is now, well established that during the evolution of tumor new cellular clones could be emerged which differ genetically from the molecular signature of tumor cells evaluated at the time of initial diagnosis. This molecular evolution may further contribute to the tumor heterogeneity during the disease progression. The evaluation of the real-time molecular tumor heterogeneity requires repeated re-biopsies during the different clinical phases of NSCLC which, however, are invasive and not, always, feasible. This problem can be by-passed by the use of tumor-originating elements in the plasma and among these cellular products the isolation and analysis of cell tumor DNA (ctDNA) and the characterization of Circulating Tumor Cells (CTCs) represent important tools for identification and monitoring of molecular tumor alterations in cancer patients, representing what the investigators call "liquid biopsy". ctDNA is originated from cellular necrosis due to increased tumoral cellular turnover and cellular ischemia as well as from apoptosis of tumor cells or lysis of Circulating Tumor Cells (CTCs). On the other hand, the CTCs, which designate the cells circulating in the blood, can be detected in several tumor types, irrespectively of the clinical phase, and their detection has been correlated with disease progression and treatment resistance. Therefore, the concomitant analysis of both ctDNA and CTCs could permit to better evaluate the genetic heterogeneity of the tumor since they continuously released from tumor cells throughout the clinical course of the disease and is considered to be proportional to tumor burden and tumor progression at each time-point.
This is a multicenter, single arm, non-randomized translational research study. Patients with operable NSCLC will be enrolled in the study. Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- blood sampling
- Keywords
- NSCLC, Tumor heterogeneity, liquid biopsy, CTCs, ctDNA, NGS
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingOther
Also called primary tumor sampling after surgery, biopsy from metastatic sites in selected patetients
Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.
| Study group | Role | What they receive |
|---|---|---|
| Operable (stages I-IIIA) NSCLC | Other | For Operable (stages I-IIIA) NSCLC Patients, blood sampling and tissue samples of the primary tumor as well as the regional involved lymph nodes and, in selected patients, from biopsies from metastasis Receives: Other: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate whether the individual patient's molecular landscape of ctDNA and CTCs could be reliable biomarkers for the early prediction of disease relapse.
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by ddPCR, for a 2-year period or until PD. For each subject, molecular analysis results will be correlated with its clinical outcome in terms of time to disease progression (PFS). CTCs will be isolated based on the cell's size. CTCs isolated by ISET will be phenotypically characterized to define their proliferative, apoptotic, EMT status as well as their immune profile using antibodies and immunofluorescent staining. CTCs isolated by PARSORTIX will be analyzed for the detection of specific genetic changes present in the primary tumor (see NGS analysis of primary tumor) using either qRT-PCR or FISH analysis.
Measured: Up to 2 years
Secondary outcomes (3)
To investigate the genetic heterogeneity in resectable NSCLC
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63.
Measured: Up to 2 years
To monitor using "liquid biopsy" the tumor clonal evolution during the post operation period and define a correlation between the genotype of the primary tumor and the emergence of molecularly different clones
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD.
Measured: Up to 2 years
To investigate the potential of longitudinal "liquid biopsy" to predict the genetic profile of metastasis
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by droplet digital Polymerase Chain Reaction (ddPCR), for a 2-year period or until PD. Moreover, in patients where metastasis re-biopsy is feasible the metastasis tumor will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the set of genes mentioned above. Correlation between the molecular analysis of the primary tumor, the ctDNA and the metastasis tumor will reveal whether longitudinal liquid biopsy can predict the metastasis genetic profile.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2018
- Study start5 Jan 2018
- Primary completion1 Dec 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hellenic Oncology Research Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Athanasios Kotsakis, MD, PhD, Principal investigator, Chairman of the Lung Cancer Working Group of the HORG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03771404
- Sponsor's protocol ID
- CT/17.01
- Status last verified
- Dec 2018
- First submitted
- 14 Nov 2018
- Last updated
- 11 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Non-small Cell Lung Carcinoma Genetic Heterogeneity in Patients With Operable Early Stage Disease and Prediction of Clinical Relapse Using a Personalized "Liquid Biopsy"
- ClinicalTrials.gov ID
- NCT03771404
- Acronym / sponsor ID
- CT/17.01
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- NSCLC, Tumor heterogeneity, liquid biopsy, CTCs, ctDNA, NGS
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Hellenic Oncology Research GroupUniversity, hospital or other
- Study start
- 5 Jan 2018 (actual)
- Primary completion
- 1 Dec 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 11 Dec 2018 (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 purpose of his study is to investigate the intra tumor heterogeneity of the primary tumor and the involved lymph nodes from patients with resectable NSCLC, to detect primary tumor genetic alternations using "liquid biopsy" during the patients' clinical follow up and to correlate the "liquid biopsy" information with the disease recurrence.
Detailed description
Lung cancer is the most common cancer in the world. In operable early stage patients NSCLS can be curable, but even after complete primary tumor resection, about 45% of early stage patients develop local or distant recurrence within 8-18 months. Recent studies have established that targeted therapies may fail to cure the disease because of tumor heterogeneity. The presence of genetic heterogeneity in different portions of a tumor have demonstrated its importance in tumor biology suggesting that pre-existing genetically different sub clones may be selected by therapy or differentially involved in the metastatic process, leading to treatment failure.
The relationship of tumor heterogeneity with the poor clinical outcome suggests that its assessment could provide interesting and useful clinical information, especially, in terms of prognosis and treatment selection. It is now, well established that during the evolution of tumor new cellular clones could be emerged which differ genetically from the molecular signature of tumor cells evaluated at the time of initial diagnosis. This molecular evolution may further contribute to the tumor heterogeneity during the disease progression. The evaluation of the real-time molecular tumor heterogeneity requires repeated re-biopsies during the different clinical phases of NSCLC which, however, are invasive and not, always, feasible. This problem can be by-passed by the use of tumor-originating elements in the plasma and among these cellular products the isolation and analysis of cell tumor DNA (ctDNA) and the characterization of Circulating Tumor Cells (CTCs) represent important tools for identification and monitoring of molecular tumor alterations in cancer patients, representing what the investigators call "liquid biopsy". ctDNA is originated from cellular necrosis due to increased tumoral cellular turnover and cellular ischemia as well as from apoptosis of tumor cells or lysis of Circulating Tumor Cells (CTCs). On the other hand, the CTCs, which designate the cells circulating in the blood, can be detected in several tumor types, irrespectively of the clinical phase, and their detection has been correlated with disease progression and treatment resistance. Therefore, the concomitant analysis of both ctDNA and CTCs could permit to better evaluate the genetic heterogeneity of the tumor since they continuously released from tumor cells throughout the clinical course of the disease and is considered to be proportional to tumor burden and tumor progression at each time-point.
This is a multicenter, single arm, non-randomized translational research study. Patients with operable NSCLC will be enrolled in the study. Patients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Operable (stages I-IIIA) NSCLC | Other | Other: blood samplingFor Operable (stages I-IIIA) NSCLC Patients, blood sampling and tissue samples of the primary tumor as well as the regional involved lymph nodes and, in selected patients, from biopsies from metastasis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed NSCLC (adenocarcinoma and squamous cell carcinoma).
- Age ≥ 18 years
- Operable (stages I-IIIA) NSCLC
- Patients with signed written informed consent obtained according to local guidelines
Key exclusion criteria (3 listed)
- Patients < 18 years
- Patients with non operable NSCLC (regardless of disease stage)
- Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator
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 |
|---|---|---|
| blood samplingAlso: primary tumor sampling after surgery, biopsy from metastatic sites in selected patetientsPatients' peripheral blood will be obtained before the surgical excision of the primary tumor as well as 1-month post-op and every 3-6 months thereafter until disease progression and upon disease relapse for the evaluation of ctDNA and CTCs. Different sites of the primary tumor as well as the regional involved lymph nodes and, in selected patients, biopsies from metastatic sites will be genotyped by NGS as well. | Other | Operable (stages I-IIIA) NSCLC |
Primary outcome
To evaluate whether the individual patient's molecular landscape of ctDNA and CTCs could be reliable biomarkers for the early prediction of disease relapse.
Time frame: Up to 2 years
The initial tumor of all patients will be submitted to Next Generation Sequencing (NGS) in order to detect mutations and copy-number variations to the following set of genes: AKT1, KRAS, NRAS, BRAF, DDR2, EGFR, FGFR1, ERBB2 (HER2), MEK1, MET, PIK3CA, PTEN, TP53, MDM2, SOX2 and P63. Detected mutations will be monitored longitudinally in ctDNA from patient's blood samples by ddPCR, for a 2-year period or until PD. For each subject, molecular analysis results will be correlated with its clinical outcome in terms of time to disease progression (PFS). CTCs will be isolated based on the cell's size. CTCs isolated by ISET will be phenotypically characterized to define their proliferative, apoptotic, EMT status as well as their immune profile using antibodies and immunofluorescent staining. CTCs isolated by PARSORTIX will be analyzed for the detection of specific genetic changes present in the primary tumor (see NGS analysis of primary tumor) using either qRT-PCR or FISH analysis.
3 secondary outcomes
To investigate the genetic heterogeneity in resectable NSCLC
Time frame: Up to 2 years
To monitor using "liquid biopsy" the tumor clonal evolution during the post operation period and define a correlation between the genotype of the primary tumor and the emergence of molecularly different clones
Time frame: Up to 2 years
To investigate the potential of longitudinal "liquid biopsy" to predict the genetic profile of metastasis
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2018.
- 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.
Athanasios Kotsakis, MD, PhD principal investigator
Chairman of the Lung Cancer Working Group of the HORG
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sampling in people with Non Small Cell Lung Cancer, run by Hellenic Oncology Research Group at 6 sites in Greece.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 11 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Greece. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vassilis Georgoulias, MD, PhD (+302106448450, georgulv@otenet.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate whether the individual patient's molecular landscape of ctDNA and CTCs could be reliable biomarkers for the early prediction of disease relapse. (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2018.