Implementing Circulating Tumor DNA Analysis at Initial Diagnosis to Improve Management of Advanced NSCLC Patients (CIRCULAR)

Implementing Circulating Tumor DNA Analysis at Initial Diagnosis to Improve Management of Advanced Non-small Cell Lung Cancer Patients (NSCLC)

Multicenter prospective cohort study aiming to evaluate the detection rate of EGFR gene mutation in patients with advanced NSCLC in a real-word clinical setting, based on liquid biopsy and tissue analyses.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer; Advanced Solid Tumor
• Intervention / Treatment: Diagnostic test: EGFR gene mutation analysis on liquid biopsy

Detailed Description

This a multicenter prospective cohort study. This study will be proposed to newly diagnosed advanced NSCLC patients. For included patients, archived paraffin embedded tumor tissue will be used for sequencing ; and blood sample will be collected for research purpose (plasma DNA collection and sequencing).

Both tissue and liquid biopsy samples will follow usual processes and will be sent to the Molecular Pathology laboratory of the Investigation center.

• Study Type: Interventional
• Enrollment (Actual): 581
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49000
    • Institut de Cancérologie de l'Ouest - Site Paul Papin
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lille, France, 59037
    • Chru Lille
  • Lyon, France, 69002
    • Hospices Civils de Lyon
  • Nice, France, 06000
    • CHU Nice-Hopital de Cimiel
  • Paris, France, 75248
    • Institut Curie
  • Poitiers, France, 86021
    • CHU Poitiers
  • Rennes, France, 35033
    • CHU De Rennes - Hôpital Pontchaillou
  • Strasbourg, France, 67091
    • CHU Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged ≥ 18 years at time of proposal study,
2. Histologically confirmed non-small cell lung carcinoma,
3. No previous treatment for NSCLC,
4. Indication to EGFR status determination following HAS recommendation,
5. Voluntary signed and dated written informed consent prior to any study specific procedure
6. Patients with a social security in compliance with the French Law.

Exclusion Criteria:

1. Treatment for advanced NSCLC started before liquid biopsy sampling.
2. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All patients; For all patients, blood sample will be collected at inclusion (liquid biopsy) for sequencing. As per standard management, for all of these patients, EGFR gene mutation will be also analyzed on archived tumor sample.	Diagnostic test: EGFR gene mutation analysis on liquid biopsy; Blood samples will be collected at inclusion for plasma DNA collection and analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the detection rate of patients with an EGFR actionable alteration when using the combination of two diagnostic procedures which include liquid biopsy analysis (by droplet digital PCR or allele specific PCR) and tissue analysis	Resuls of each EGFR diagnostic procedure will be categorized as EGFR positive in case of the presence of an EGFR actionnable alteration ; as EGFR negative in case of the absence of an EGFR actionnable alteration ; or nor interpretable. A patient will be considered to have an EGFR actionable alteration if the mutation has been detected on the sequencing of tumor tissue OR if it has been detected on the liquid biopsy procedure	within 3 weeks after signature of informed consent

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The detection rate of patients with an EGFR actionable alteration based on the use of liquid biopsy analysis only	A patient will be considered to have an EGFR actionable alteration (EGFR+) detected by the liquid biopsy analysis if an EGFR actionable alteration is identified based on the liquid biopsy analysis	within 3 weeks after signature of informed consent
The detection rate of patients with an EGFR actionable alteration based on tissue analysis only	A patient will be considered to have an EGFR actionable alteration (EGFR+) detected by tissue analysis if an EGFR actionable alteration is identified based on the sequencing of tumor tissue	within 3 weeks after signature of informed consent
The concordance and discordance rates between the two procedures	Concordance is defined whenever results of both techniques are identical (i.e. EGFR+ for both techniques or EGFR- for both techniques). Discordance is defined whenever results of both techniques are different.	within 3 weeks after signature of informed consent
The failure rate for each procedure and reasons of failure (insufficient DNA quantity, poor DNA quality, insufficient tissue quantity, poor tissue quality, analytical failure)	• Failure of a procedure (sequencing of tumor tissue or liquid biopsy) is defined whenever the procedure fails to provide an interpretable result (Reasons for failure will be collected, i.e. insufficient DNA quantity, poor DNA quality, insufficient DNA/tissue quantity, poor DNA/tissue quality, analytical failure)	within 3 weeks after signature of informed consent
Delay to obtain sequencing results	The delay between the date of the signature of the informed consent and the date of availability of the results for each procedure	within 3 weeks after signature of informed consent
Delay for treatment initiation	The delay between the date of sample collection and the date of treatment initiation	within 3 months after signature of informed consent

Collaborators and Investigators

• Sponsor: Institut Bergonié
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): January 17, 2026
• Study Completion (Actual): January 17, 2026

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; liquid biopsy; EGFR detection
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: IB 2021-02; 2021-A00685-36 (Other Identifier: ANSM IDRCB Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No