Clinical trial NCT05221372: ProSpecTive sAmpling in dRiver muTation Pulmonary Oncology Patients on Tyrosine Kinase Inhibitors (START-TKI)
Official title: proSpecTive sAmpling in dRiver muTation Pulmonary Oncology Patients on Tyrosine Kinase Inhibitors
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non Small Cell Lung Cancer
Liquid Biopsy
Tyrosine Kinase Inhibitor
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2022-02-03
Enrollment: 1300
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: Adult patients with non-small cell lung cancer treated with a tyrosine kinase inhibitor

Brief summary: The study is perfomed with adult patients with non-small cell lung cancer treated with tyrosine kinase inhibitor. The objective is to collect repeated samples of blood from patients (starting) on a tyrosine kinase inhibitor, for liquid mutation testing, and pharmacokinetic analysis.

Detailed description: This is an observational study in pulmonary oncology patients treated with TKI. Ideally before start of therapy, at week 4, 8 12, and then every 4-8 weeks (following the standard of care clinical pathways local guidelines) extra tubes of blood will be collected during blood withdrawal planned for standard-of-care. When a TKI switch takes place, patients receive a new study number and the blood collection will be continued following standard-of-care. Sampling will be performed during steady-state in working hours before next ingestion of TKI (the regular morning dose will need to be postponed until after blood withdrawal).

The moment of blood withdrawal after start of therapy and after last dosage of TKI will be registered.

At the time of progression the current standard of care is to perform a rebiopsy, to identify the resistance mechanism and determine the next appropriate systemic therapy for a patient. Some mechanisms can only be determined on a biopsy specimen (e.g. transformation to SCLC, MET amplification FISH). This study is observational and will not interfere with the current standard practice, therefore the treating physician is free to determine the indication for and possibility of a rebiopsy. However, when a biopsy is taken as standard of care, we will also draw an extra blood sample on the day of the biopsy (preferably during standard preprocedural coagulation status laboratory investigations) and use a portion of the biopsy for a fresh frozen specimen, as evolving molecular investigations (like RNA analysis) often need fresh non-fixed material to obtain reliable results.

Four to five core biopsies will be obtained for further analysis. Half of the obtained biopsy material will be stored in formalin according to local standard procedures, while the other half will be fresh frozen according to local standard procedures and stored for further analysis.

When the treating physician needs to take additional tissue or liquid (e.g. pleural fluid, liquor) for investigations following standard-of-care protocols, we would like to perform additional molecular and/or pharmacokinetic analysis on the residual material when applicable.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Able to understand the written informed and able to give informed consent
* Locally advanced or metastatic NSCLC with oncogenic driver mutation
* Treatment with TKI according to standard of care

Exclusion Criteria:

* Unable to draw blood for study purposes

Primary outcomes:
measure: Relative presence of primary mutation and resistance mutations in plasma levels under treatment of a small molecule kinase inhibitor until progression of disease measured in variant allele frequency
timeFrame: 10 years
measure: Plasma concentrations of the small molecule kinase inhibitor during treatment until progression of disease
timeFrame: 10 years
Secondary outcomes:
measure: Time to progression or death under treatment with small molecule kinase inhibitor
timeFrame: 10 years
measure: Overall survival
timeFrame: 10 years
measure: Pharmacokinetics of intratumoral small molecule kinase inhibitors
timeFrame: 10 years
measure: Correlation of mutation status in blood to (re)biopsy specimen results performed for standard-of-care.
timeFrame: 10 years
measure: Correlation between the BMI of the patient and mean concentration of the small molecule kinase inhibitor
timeFrame: 10 years
measure: Correlation between smoking status of the patients and mean concentration of the small molecule kinase inhibitor
timeFrame: 10 years
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
Study officials:
affiliation: Erasmus Medical Center
name: Anne-Marie Dingemans, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Steendam CMJ, Veerman GDM, Pruis MA, Atmodimedjo P, Paats MS, van der Leest C, von der Thusen JH, Yick DCY, Oomen-de Hoop E, Koolen SLW, Dinjens WNM, van Schaik RHN, Mathijssen RHJ, Aerts JGJV, Dubbink HJ, Dingemans AC. Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer. Cancers (Basel). 2020 Oct 29;12(11):3179. doi: 10.3390/cancers12113179.