ProSpecTive sAmpling in dRiver muTation Pulmonary Oncology Patients on Tyrosine Kinase Inhibitors (START-TKI)

Recruiting

• Conditions: Tyrosine Kinase Inhibitor; Non Small Cell Lung Cancer; Liquid Biopsy

• Registration Number: NCT05221372
• Lead Sponsor: Erasmus Medical Center

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.

Study Timeline

• Study Start: 2017-02-02
• Study First Submitted: 2022-01-10
• Study First Submitted QC: 2022-01-21
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-02
• Study First Posted: 2022-02-03
• Last Update Posted: 2022-02-18
• Primary Completion: 2031-01-01
• Study Completion: 2031-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1300

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Plasma concentrations of the small molecule kinase inhibitor during treatment until progression of disease	10 years	Describing the plasma concentrations over time during treatment with a small molecule kinase inhibitor by sequentially measuring mean concentrations of the small molecule kinase inhibitor.
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	10 years	Describing the plasma levels of primary mutations and resistance mutations under treatment by sequentially measuring cell free tumor DNA.; Different techniques will be used for the plasma mutation detection (ddPCR and NGS)

Secondary Outcome Measures

Name	Time	Method
Correlation of mutation status in blood to (re)biopsy specimen results performed for standard-of-care.	10 years	Concordance of detection of tumor mutations will be evaluated between ddPCR, NGS in blood, and NGS in tissue samples when available
Correlation between the BMI of the patient and mean concentration of the small molecule kinase inhibitor	10 years	Effects of BMI on PK will be explored by means of regression analysis.
Correlation between smoking status of the patients and mean concentration of the small molecule kinase inhibitor	10 years	Effects of smoking status on PK will be explored by means of regression analysis.
Overall survival	10 years	Defined as time from start of the small molecule kinase inhibitor to death.
Pharmacokinetics of intratumoral small molecule kinase inhibitors	10 years	Measuring intratumoral concentrations of small molecule kinase inhibitors on tumor biopsy taken as part of regular care
Time to progression or death under treatment with small molecule kinase inhibitor	10 years	Time to progression or death is defined as time from start of the small molecule kinase inhibitor to radiological progression (according to measurements conform RECIST v.1.1) or death.

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands