Clinical trial NCT06105177: Implementation of Up-front ctDNA Into Lung Cancer Care and Development of Liquid Biopsy-based Decision Support Models - LM² Study
Official title: Implementation of Up-front ctDNA Analysis Into Lung Cancer Care and Development of Liquid Biopsy-based Decision Support Models - the Lungmarker² Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Cancer
Keywords: lungmarker2 study
lung cancer
liquid biopsy
ctDNA
CTCs
tumormarkers
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
Collaborators: name: Eindhoven University of Technology
name: Roche BV Netherlands
name: Maxima Medical Center
name: Zuyderland Medisch Centrum
name: Maastricht University Medical Center
name: St. Anna Ziekenhuis, Geldrop, Netherlands
name: The Netherlands Cancer Institute
First posted: 2023-10-27
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Up-front ctDNA analysis is implemented into routine clinical care in the participating OncoZoN hospitals
timeFrame: Up to 3 years
measure: Evaluate the number of driver mutations detected by up-front ctDNA analysis compared to tumor NGS analysis
timeFrame: Up to 3 years
measure: Develop decision support algorithms for the diagnosis and monitoring of lung cancer patients
timeFrame: Up to 3 years
Secondary outcomes:
measure: Develop an analytical protocol for the analysis of PD-L1 expression on circulating tumor cells (CTCs) by super-resolution microscopy
timeFrame: Up to 3 years
measure: Evaluate the number of tumor NGS analyses and time to diagnosis when up-front ctDNA analysis is introduced
timeFrame: Up to 3 years
Other outcomes:
measure: A study database is filled with all relevant clinical and diagnostic information
timeFrame: Up to 3 years
Locations:
city: Heerlen
country: Netherlands
facility: Zuyderland Medical Center
state: Limburg
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
state: North Brabant
city: Geldrop
country: Netherlands
facility: St. Anna Ziekenhuis
state: North Brabant
city: Veldhoven
country: Netherlands
facility: Máxima Medisch Centrum
state: North Brabant
Study officials:
affiliation: Catharina Ziekenhuis Eindhoven
name: Volkher Scharnhorst, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
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