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

proSpecTive sAmpling in dRiver muTation Pulmonary Oncology Patients on Tyrosine Kinase Inhibitors

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.

Study Overview

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

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 Type: Observational
• Enrollment (Anticipated): 1300

Contacts and Locations

• Study Contact: Name: Anne-Marie Dingemans, MD, PhD; Phone Number: +31107040704; Email: a.dingemans@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
    • Contact: Anne-Marie Dingemans, MD, PhD; Phone Number: +31107040704; Email: a.dingemans@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with non-small cell lung cancer treated with a tyrosine kinase inhibitor

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	10 years
Plasma concentrations of the small molecule kinase inhibitor during treatment until progression of disease	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.	10 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Anne-Marie Dingemans, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Anticipated): January 1, 2031
• Study Completion (Anticipated): January 1, 2031

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NL58664.078.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No