NSCLC Heterogeneity in Early Stage Patients and Prediction of Relapse Using a Personalized "Liquid Biopsy"

NCT03771404 | Unknown

• 1 other identifier: CT/17.01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief 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 with the disease recurrence.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC; Tumor heterogeneity; liquid biopsy; CTCs; ctDNA; NGS

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (3)

• To investigate the genetic heterogeneity in resectable NSCLC

  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

  Up to 2 years

• To investigate the potential of longitudinal "liquid biopsy" to predict the genetic profile of metastasis

  Up to 2 years

Study Arms (1)

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

Other: blood sampling

Interventions

blood sampling OTHER

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.

Also known as: primary tumor sampling after surgery, biopsy from metastatic sites in selected patetients

Operable (stages I-IIIA) NSCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hellenic Oncology Research Group: lead

Study Sites (6)

2nd Pneumological Dept, GNA "Sotiria"

Athens, Attica, 11527, Greece

RECRUITING

7th Pneumological Dept, GNA "Sotiria"

Athens, Attica, 11527, Greece

RECRUITING

Thoracic Surgery Dept, GNA "Sotiria"

Athens, Attica, 11527, Greece

RECRUITING

Thoracic Surgery Clinic, "Hygeia" Hospital

Athens, Attica, 15123, Greece

NOT YET RECRUITING

Oncology Unit, 3rd Department of Medicine Athens University School of Medicine Athens, GNA "Sotiria"

Athens, 11527, Greece

RECRUITING

IASO General Hospital

Athens, Greece

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Athanasios Kotsakis, MD, PhD

  Chairman of the Lung Cancer Working Group of the HORG

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vassilis Georgoulias, MD, PhD

CONTACT

+302106448450; georgulv@otenet.gr

Efthimios Prinarakis, PhD

CONTACT

+302106448450; eprinarakis@horg.gr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: December 11, 2018
• Study Start: January 5, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 11, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (6)