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

NCT06105177 | Recruiting

• 1 other identifier: NL83276.100.22
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Lung Cancer

Keywords

lungmarker2 study; lung cancer; liquid biopsy; ctDNA; CTCs; tumormarkers

Outcome Measures

Primary Outcomes (3)

• Up-front ctDNA analysis is implemented into routine clinical care in the participating OncoZoN hospitals

  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

  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

  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 Outcomes (2)

• Develop an analytical protocol for the analysis of PD-L1 expression on circulating tumor cells (CTCs) by 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

  Up to 3 years

Other Outcomes (1)

• A study database is filled with all relevant clinical and diagnostic information

  Up to 3 years

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

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.

You may qualify if:

• Aged 18 or above and suspected of having lung cancer

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (5)

Zuyderland Medical Center

Heerlen, Limburg, 6419PC, Netherlands

NOT YET RECRUITING

Maastricht University Medical Center

Maastricht, Limburg, 6229HX, Netherlands

NOT YET RECRUITING

Catharina Ziekenhuis Eindhoven

Eindhoven, North Brabant, 5623EJ, Netherlands

RECRUITING

St. Anna Ziekenhuis

Geldrop, North Brabant, 5664EH, Netherlands

NOT YET RECRUITING

Máxima Medisch Centrum

Veldhoven, North Brabant, 5504DB, Netherlands

NOT YET RECRUITING

Related Publications (35)

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Related Links

• de Kock RPPAW. Tumor markers in diagnosis and therapy monitoring of lung cancer. Technische Universiteit Eindhoven; 2021.

Biospecimen

Retention: SAMPLES WITH DNA

* Whole blood drawn into serum tubes for the measurement of tumormarkers (CA125, CA15.3, CEA, CYFRA 21.1, HE-4, NSE, proGRP, SCCA) * Whole blood drawn into cell preservation tubes for ctDNA analysis and isolation of circulating tumor cells (CTCs)

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Volkher Scharnhorst, Prof.Dr.

  Catharina Ziekenhuis Eindhoven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Cao, MSc

CONTACT

+31402398644; hao.cao@catharinaziekenhuis.nl

Volkher Scharnhorst, Prof.Dr.

CONTACT

+31402398640; volkher.scharnhorst@catharinaziekenhuis.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. (Clinical Chemist)

Study Record Dates

• First Submitted: October 17, 2023
• First Posted: October 27, 2023
• Study Start: October 31, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

NL (5)