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

Lung Cancer Clinical Trial

— LM2  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06105177
• Other study ID #: NL83276.100.22
• Status: Not yet recruiting
• Start date: October 2023
• Est. completion date: July 2026

Study information

• Verified date: October 2023
• Source: Catharina Ziekenhuis Eindhoven
• Contact: Hao Cao, MSc
• Phone: +31402398644
• Email: hao.cao[@]catharinaziekenhuis.nl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 800
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Locations

Country	Name	City	State
Netherlands	Catharina Ziekenhuis Eindhoven	Eindhoven	North Brabant
Netherlands	St. Anna Ziekenhuis	Geldrop	North Brabant
Netherlands	Zuyderland Medical Center	Heerlen	Limburg
Netherlands	Maastricht University Medical Center	Maastricht	Limburg
Netherlands	Máxima Medisch Centrum	Veldhoven	North Brabant

Sponsors (8)

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

Country where clinical trial is conducted

Netherlands, 

References & Publications (35)

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	A study database is filled with all relevant clinical and diagnostic information	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
Primary	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
Primary	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
Primary	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	Develop an analytical protocol for the analysis of PD-L1 expression on circulating tumor cells (CTCs) by super-resolution microscopy	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
Secondary	Evaluate the number of tumor NGS analyses and time to diagnosis when up-front ctDNA analysis is introduced	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

External Links

•   de Kock RPPAW. Tumor markers in diagnosis and therapy monitoring of lung cancer. Technische Universiteit Eindhoven; 2021.
•   Dutch Federation of Medical Specialists. Non-Small Cell Lung Cancer
•   Dutch Federation of Medical Specialists. Small Cell Lung Cancer