Implementation of Up-front ctDNA Into Lung Cancer Care and Development of Liquid Biopsy-based Decision Support Models - LM² Study (LM2)

October 23, 2023 updated by: Volkher Scharnhorst, Catharina Ziekenhuis Eindhoven

Implementation of Up-front ctDNA Analysis Into Lung Cancer Care and Development of Liquid Biopsy-based Decision Support Models - the Lungmarker² Study

Despite scientific evidence, use of liquid biopsy (LB) in diagnosis and monitoring of lung cancer (LC) is limited since it requires major changes in diagnostic and care pathways. Analyzing tumor markers (TMs), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood (LB) can inform about the nature of the tumor, the most appropriate therapy, therapy response and resistance.

Lungmarker2 is a multicenter, prospective, implementation and diagnostic cohort study. This study aims to implement up-front ctDNA analysis ('plasma first approach') into routine diagnostic work-up of all advanced stage LC patients in the Southeast of the Netherlands (the participating hospitals in the OncoZON region). Thereby, additional information about the molecular make-up of the tumor becomes available, the number of tissue Next-Generation Sequencing (NGS) analyses will decrease and time to therapeutic decision making is shortened. Next, using ctDNA, TM and other information, multi-parametric decision support models are built and validated that may support diagnosis, predict the outcome of the next imaging procedure and progression-free survival during follow-up. The final goal is to develop a super-resolution microscopy test that can detect PD-L1 expression on CTCs.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

RATIONALE: Despite scientific evidence, use of liquid biopsy (LB) in diagnosis and monitoring of lung cancer (LC) is limited since it requires major changes in diagnostic and care pathways. Analyzing tumor markers (TMs), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood (LB) can inform about the nature of the tumor, the most appropriate therapy, therapy response and resistance.

OBJECTIVE: To implement up-front ctDNA analysis ('plasma first approach') into routine diagnostic work-up of all advanced stage LC patients in the Southeast of the Netherlands (the participating hospitals in the OncoZON region) and to thereby validate that significantly more information about the molecular make-up of the tumor becomes available by introduction of up-front ctDNA. To establish that the number of tissue NGS analyses decreases and time to therapeutic decision making is shortened. To build and to validate, using ctDNA, TM and other information, multiparametric decision support models that may support diagnosis, predict the outcome of the next imaging procedure and survival during follow up. The final goal is to develop a super-resolution microscopy test that can detect PD-L1 expression on CTCs.

STUDY DESIGN: Multicenter, prospective, implementation and diagnostic cohort study.

STUDY POPULATION: 800 patients suspected of having lung cancer.

MAIN STUDY PARAMETERS/ENDPOINTS: ctDNA analysis, as additional source of genetic information, has been integrated into the diagnostic workup of LC patients and the medical benefits thereof are quantified, e.g. a significant higher percentage of patients with a driver mutation is identified by introduction of the plasma first approach. Multiparametric decision support algorithms based on imaging, TM and ctDNA analyses that identify small-cell LC (SCLC) and non-small-cell LC (NSCLC) have been developed and validated. Multiparametric decision support models have been developed that enable patient-specific timing of imaging procedures and predict survival during follow-up of LC patients. A super-resolution microscopy test for PD-L1 is developed and correlation with tumor tissue PD-L1 expression has been established.

NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT AND GROUP RELATEDNESS: At diagnosis, an extra 10 mL of blood are drawn during a routine venipuncture. Patients with advanced stage LC (stage IIIb/c or IV) undergo an extra venipuncture (40 mL).The longest follow up period for a patient is 36 months with a maximum of 20 blood draws. The volume per draw ranges from 10-40 mL. The risks of a venipuncture are negligible and the burden minimal. Those patients for whom a targetable mutation is found by ctDNA analysis benefit from the advantages of targeted therapy, i.e. better survival and less side effects of the treatment.

Study Type

Observational

Enrollment (Estimated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Limburg
      • Heerlen, Limburg, Netherlands, 6419PC
        • Zuyderland Medical Center
        • Contact:
          • Michiel Gronenschild, MD
      • Maastricht, Limburg, Netherlands, 6229HX
        • Maastricht University Medical Center
        • Contact:
          • Lizza Hendriks, MD, PhD
    • North Brabant
      • Eindhoven, North Brabant, Netherlands, 5623EJ
      • Geldrop, North Brabant, Netherlands, 5664EH
        • St. Anna Ziekenhuis
        • Contact:
          • Gerben Stege, MD, PhD
      • Veldhoven, North Brabant, Netherlands, 5504DB
        • Maxima Medisch Centrum
        • Contact:
          • Magdolen El Soud-Youssef, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

800 individuals, >18 years of age, suspected of lung cancer and referred to a lung physician in one of the participating centers are included in the study.

Description

Inclusion Criteria:

  • Aged 18 or above and suspected of having lung cancer

Exclusion Criteria:

  • Presence of another malignant tumor, i.e. diagnosed with a tumor in the past 5 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Up-front ctDNA analysis is implemented into routine clinical care in the participating OncoZoN hospitals
Time Frame: Up to 3 years
After the Lungmarker2 study has proven up-front ctDNA analysis to be feasible and successful for diagnosis and monitoring of lung cancer, hospitals participating in this project will adopt this as routine practice. Up-front ctDNA analysis will be adopted by the other OncoZON hospitals outside the consortium through transfer of the clinical practice during the regular tumor board meetings where shared care decisions are made for individual patients.
Up to 3 years
Evaluate the number of driver mutations detected by up-front ctDNA analysis compared to tumor NGS analysis
Time Frame: Up to 3 years
Determine and compare the number of driver mutations detected by up-front ctDNA analysis with the number of driver mutations detected by tumor NGS analysis.
Up to 3 years
Develop decision support algorithms for the diagnosis and monitoring of lung cancer patients
Time Frame: Up to 3 years

Develop decision support algorithms using information from CT scans, measured tumor markers (CA125, CA15.3, CEA, CYFRA 21.1, HE-4, NSE, proGRP, SCCA) and ctDNA analysis to identify small-cell lung cancer and non-small-cell lung cancer patients (classification, diagnosis).

Develop decision support algorithms to predict therapy response, expressed as a threshold for durable clinical benefit: the progression free survival (PFS) at 6 months (as probability %), in lung cancer patients (monitoring).

Different metrics regarding model performances will be reported: area under the receiver operating characteristic curve (AUC), area under the precision- recall curve (AUC-PR), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV).
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Develop an analytical protocol for the analysis of PD-L1 expression on circulating tumor cells (CTCs) by super-resolution microscopy
Time Frame: Up to 3 years
Develop an analytical protocol for the isolation of CTCs from whole blood samples (measured as the number of cells per mL) and to quantify PD-L1 expression (reported as a percentage on a scale of 0% to 100%) on the isolated CTCs using super-resolution microscopy.
Up to 3 years
Evaluate the number of tumor NGS analyses and time to diagnosis when up-front ctDNA analysis is introduced
Time Frame: Up to 3 years
Determine the time to diagnosis (in days) of lung cancer (e.g., time between first visit at lung physician and the diagnosis) when using up-front ctDNA analysis compared to tumor NGS analysis, and determine the number of tumor NGS analyses that can be replaced by up-front ctDNA analysis.
Up to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
A study database is filled with all relevant clinical and diagnostic information
Time Frame: Up to 3 years
For the Lungmarker2 study, all information will be entered into the study database (Research manager) by personnel of the participating hospitals (research nurse, physician or lung oncology nurse) using a digital CRF. Research manager offers eCRF possibilities and enables safe and anonymous data collection, storage and management. The data collected include patient data, detailed results of diagnostic procedures and tests including imaging procedures, treatment regime and response evaluation.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Catharina Ziekenhuis Eindhoven

Collaborators

Maastricht University Medical Center
The Netherlands Cancer Institute
Maxima Medical Center
Zuyderland Medisch Centrum
Eindhoven University of Technology
Roche BV Netherlands
St. Anna Ziekenhuis, Geldrop, Netherlands

Investigators

  • Principal Investigator: Volkher Scharnhorst, Prof.Dr., Catharina Ziekenhuis Eindhoven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2023

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

October 17, 2023

First Submitted That Met QC Criteria

October 23, 2023

First Posted (Actual)

October 27, 2023

Study Record Updates

Last Update Posted (Actual)

October 27, 2023

Last Update Submitted That Met QC Criteria

October 23, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL83276.100.22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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