Impact of Liquid Biopsy on the Therapeutic Pathway for Lung Cancer: Advancing the Molecular Characterization of Patients With Advanced Lung Adenocarcinoma by Integrating Liquid Biopsy Into the Early Stages of the Diagnostic and Therapeutic Pathway

NCT07649629 | Recruiting

• 1 other identifier: RS348/2025
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter pilot observational study aims to assess the feasibility of introducing liquid biopsy at an early stage of the diagnostic pathway for patients with suspected advanced non-small cell lung cancer (NSCLC). Liquid biopsy is a minimally invasive blood test that can detect tumor-related genetic alterations in circulating nucleic acids. The study will evaluate whether this approach can provide molecular information more rapidly than standard tissue-based testing and how closely the results obtained from blood samples match those obtained from tumor tissue. Approximately 70 adult patients with radiological evidence of locally advanced or metastatic lung cancer will be enrolled. Participants will undergo a blood draw for liquid biopsy and will continue to follow the standard diagnostic pathway, including tissue biopsy or cytological sampling when indicated. The results generated within the study are intended for research purposes and will not replace standard diagnostic procedures or independently determine treatment decisions. The findings will be used to identify practical and methodological issues and to support the design of future clinical studies on the plasma-first approach.

Conditions

Advanced Non-small Cell Lung Cancer (NSCLC)

Keywords

Lung Cancer; Liquid biopsy; Plasma-first approach; Non-small cell lung cancer; NSCLC; ctDNA; ctRNA; NGS; Molecular profiling; Tumor fraction; Actionable genomic alterations; Targeted therapy; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Feasibility of establishing a structured plasma-first molecular profiling dataset

  Proportion of enrolled participants with a complete structured dataset including liquid biopsy results, tissue-based diagnostic and molecular profiling results, and relevant clinical data required for the feasibility assessment of the plasma-first approach.

  Up to 18 months

Secondary Outcomes (5)

• Turnaround time for plasma-based molecular profiling

  Up to 7 days from blood collection

• Proportion of participants with informative liquid biopsy results

  Up to 30 days from enrollment

• Concordance between plasma-based and tissue-based molecular profiling

  Up to 30 days from enrollment

• Tumor fraction in plasma samples

  Up to 30 days from blood collection

• Analytical performance of two NGS-based plasma profiling approaches

  Up to 18 months

Study Arms (1)

Prospective Plasma-First NSCLC Cohort

Adult patients with radiological suspicion of locally advanced non-small cell lung cancer (NSCLC) not suitable for locoregional treatment, or metastatic NSCLC, will be enrolled before completion of the standard diagnostic pathway. Participants will undergo a peripheral blood draw for liquid biopsy within one week of the first clinical assessment. Plasma-derived circulating nucleic acids will be analyzed using next-generation sequencing (NGS) to evaluate molecular alterations, turnaround time, concordance with tissue-based profiling, and tumor fraction. All participants will continue the standard diagnostic pathway of the enrolling center, including tissue biopsy or cytological sampling, histopathological diagnosis, PD-L1 assessment, and tissue-based molecular testing. No investigational treatment is assigned, and study procedures will not independently determine treatment decisions.

Diagnostic Test: Plasma-based liquid biopsy

Interventions

Plasma-based liquid biopsy DIAGNOSTIC_TEST

Participants will undergo a peripheral blood draw for plasma-based liquid biopsy within one week of the first clinical assessment. Circulating cell-free nucleic acids extracted from plasma will be analyzed using next-generation sequencing (NGS) to identify molecular alterations and evaluate turnaround time, concordance with tissue-based molecular profiling, and tumor fraction. The liquid biopsy is performed for research purposes within this pilot observational study. Participants will continue the standard diagnostic pathway of the enrolling center, including tissue biopsy or cytological sampling, histopathological diagnosis, PD-L1 assessment, and standard tissue-based molecular testing. The study procedure will not independently determine treatment decisions.

Prospective Plasma-First NSCLC Cohort

Eligibility Criteria

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

Study Population

The study population includes adult patients with radiological suspicion of locally advanced lung cancer not suitable for locoregional treatment or metastatic lung cancer. Participants are enrolled before completion of the standard diagnostic pathway, when tissue biopsy or cytological sampling is planned but not yet performed, or has already been performed without an available histopathological diagnosis of NSCLC. Eligible patients are recruited at participating centers during thoracic surgery assessment or the first oncology visit and undergo plasma-based liquid biopsy while continuing the standard diagnostic pathway.

You may qualify if:

• Age ≥ 18 years.
• Radiological suspicion of locally advanced lung cancer not amenable to locoregional treatment or metastatic lung cancer (stage III-IV).
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Tissue biopsy and/or cytological sampling planned but not yet performed, or already performed without an available histopathological diagnosis of non-small cell lung cancer (NSCLC).
• Written informed consent for study participation and personal data processing obtained before any study-specific procedure.

You may not qualify if:

• Previous or current history of non-small cell lung cancer (NSCLC).
• Histopathological diagnosis of NSCLC already available following tissue biopsy.
• Eligibility for surgical removal of tumor tissue.
• Ongoing or previous systemic oncological treatment for lung cancer.

Sponsors & Collaborators

• Regina Elena Cancer Institute: lead

Study Sites (1)

IFO-IRE, Istituto Nazionale Tumori Regina Elena

Roma, RM, 00144, Italy

RECRUITING

Related Publications (4)

• Low SK, Ariyasu R, Uchibori K, Hayashi R, Chan HT, Chin YM, Akita T, Harutani Y, Kiritani A, Tsugitomi R, Manabe R, Ogusu S, Amino Y, Kitazono S, Yanagitani N, Nakamura Y, Nishio M. Rapid genomic profiling of circulating tumor DNA in non-small cell lung cancer using Oncomine Precision Assay with Genexus integrated sequencer. Transl Lung Cancer Res. 2022 May;11(5):711-721. doi: 10.21037/tlcr-21-981.

  PMID: 35693289 BACKGROUND

• Husain H, Pavlick DC, Fendler BJ, Madison RW, Decker B, Gjoerup O, Parachoniak CA, McLaughlin-Drubin M, Erlich RL, Schrock AB, Frampton GM, Das Thakur M, Oxnard GR, Tukachinsky H. Tumor Fraction Correlates With Detection of Actionable Variants Across > 23,000 Circulating Tumor DNA Samples. JCO Precis Oncol. 2022 Oct;6:e2200261. doi: 10.1200/PO.22.00261.

  PMID: 36265119 BACKGROUND

• Rolfo C, Mack P, Scagliotti GV, Aggarwal C, Arcila ME, Barlesi F, Bivona T, Diehn M, Dive C, Dziadziuszko R, Leighl N, Malapelle U, Mok T, Peled N, Raez LE, Sequist L, Sholl L, Swanton C, Abbosh C, Tan D, Wakelee H, Wistuba I, Bunn R, Freeman-Daily J, Wynes M, Belani C, Mitsudomi T, Gandara D. Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer. J Thorac Oncol. 2021 Oct;16(10):1647-1662. doi: 10.1016/j.jtho.2021.06.017. Epub 2021 Jul 8.

  PMID: 34246791 BACKGROUND

• Garcia-Pardo M, Czarnecka K, Law JH, Salvarrey A, Fernandes R, Fan J, Corke L, Waddell TK, Yasufuku K, Donahoe LL, Pierre A, Le LW, Ghumman N, Liu G, Shepherd FA, Bradbury P, Sacher A, Stockley T, Pal P, Rogalla P, Tsao MS, Leighl NB. Plasma-first: accelerating lung cancer diagnosis and molecular profiling through liquid biopsy. Ther Adv Med Oncol. 2022 Sep 20;14:17588359221126151. doi: 10.1177/17588359221126151. eCollection 2022.

  PMID: 36158638 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Residual plasma samples obtained from peripheral blood draws will be retained and stored at -80°C at the enrolling centers. These samples may contain circulating cell-free nucleic acids, including cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and circulating tumor RNA (ctRNA), and may be used for future research analyses compatible with the purposes of the original collection.

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Study Officials

• Federico Cappuzzo, MD

  IFO-IRE, Istituto Nazionale Tumori Regina Elena

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maristella Giammaruco, MD

CONTACT

+39 06 5266 5698; maristella.giammaruco@ifo.it

Simonetta Buglioni, Biology

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 16, 2026
• Study Start: September 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)