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

NCT ID: NCT03771404

Last Updated: 2018-12-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-05
• Study Completion Date: 2021-12-01

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.

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

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Operable (stages I-IIIA) NSCLC

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

Group Type: OTHER

blood sampling

Intervention Type: 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.

Interventions

blood sampling

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.

Intervention Type: OTHER

Other Intervention Names

primary tumor sampling after surgery; biopsy from metastatic sites in selected patetients

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hellenic Oncology Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Athanasios Kotsakis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chairman of the Lung Cancer Working Group of the HORG

Locations

2nd Pneumological Dept, GNA "Sotiria"

Athens, Attica, Greece

Site Status: RECRUITING

7th Pneumological Dept, GNA "Sotiria"

Athens, Attica, Greece

Site Status: RECRUITING

Thoracic Surgery Dept, GNA "Sotiria"

Athens, Attica, Greece

Site Status: RECRUITING

Thoracic Surgery Clinic, "Hygeia" Hospital

Athens, Attica, Greece

Site Status: NOT_YET_RECRUITING

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

Athens, , Greece

Site Status: RECRUITING

IASO General Hospital

Athens, , Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Vassilis Georgoulias, MD, PhD

Role: CONTACT

Phone: +302106448450

Email: georgulv@otenet.gr

Efthimios Prinarakis, PhD

Role: CONTACT

Phone: +302106448450

Email: eprinarakis@horg.gr

Facility Contacts

Aggeliki Rapti, MD

Role: primary

Mina Gaga, MD

Role: primary

Evaggelos Sepsas, MD

Role: primary

Kosmas Iliadis, MD

Role: primary

Konstantinos Syrigos, MD,PhD,FCCP

Role: primary

Vassilis Georgoulias, MD, PhD

Role: primary

Other Identifiers

CT/17.01

Identifier Type: -

Identifier Source: org_study_id