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Non Small Cell Lung CancerSTART-TKINCT05221372

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

An observational study of Non Small Cell Lung Cancer and Liquid Biopsy, run by Erasmus Medical Center at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
How many people
1,300 participants
Where
1 siteNetherlands
Study dates
2 Feb 2017to 1 Jan 2031
How long will I take part?
10 Years
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • 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

Who cannot join

  • Unable to draw blood for study purposes

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Anne-Marie Dingemans, MD, PhD contact

+31107040704

a.dingemans@erasmusmc.nl

Netherlands1 site, 1 recruiting

  • Erasmus MC

    Rotterdam

    Anne-Marie Dingemans, MD, PhD, +31107040704, a.dingemans@erasmusmc.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: 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.

Read the 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.

Medical subject headings
Carcinoma, Non-Small-Cell Lung

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 10 years

  2. 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.

    Measured: 10 years

Secondary outcomes (6)

  1. 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.

    Measured: 10 years

  2. Overall survival

    Defined as time from start of the small molecule kinase inhibitor to death.

    Measured: 10 years

  3. Pharmacokinetics of intratumoral small molecule kinase inhibitors

    Measuring intratumoral concentrations of small molecule kinase inhibitors on tumor biopsy taken as part of regular care

    Measured: 10 years

  4. 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

    Measured: 10 years

  5. 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.

    Measured: 10 years

  6. 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.

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2022
  2. Study start2 Feb 2017
  3. Primary completion1 Jan 2031 (estimated)
  4. Study completion1 Jan 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
1,300 participants (estimated)
Target duration
10 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT05221372
Sponsor's protocol ID
NL58664.078.16
Acronym
START-TKI
Status last verified
Feb 2022
First submitted
10 Jan 2022
Last updated
18 Feb 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

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.

    PubMed 33138052

  • Ernst SM, van Marion R, Atmodimedjo PN, de Jonge E, Mathijssen RHJ, Paats MS, de Bruijn P, Koolen SL, von der Thusen JH, Aerts JGJV, van Schaik RHN, Dubbink HJ, Dingemans AC. Clinical Utility of Circulating Tumor DNA in Patients With Advanced KRASG12C-Mutated NSCLC Treated With Sotorasib. J Thorac Oncol. 2024 Jul;19(7):995-1006. doi: 10.1016/j.jtho.2024.04.007. Epub 2024 Apr 12.

    PubMed 38615940

  • Ernst SM, Uzun S, Paats MS, van Marion R, Atmodimedjo PN, de Jonge E, van Schaik RHN, Aerts JGJV, von der Thusen JH, Dubbink HJ, Dingemans AC. Efficacy and Tolerability of Osimertinib and Sotorasib Combination Treatment for Osimertinib Resistance Caused by KRAS G12C Mutation: A Report of Two Cases. JCO Precis Oncol. 2023 Sep;7:e2300451. doi: 10.1200/PO.23.00451.

    PubMed 38096473

Questions about this trial

What is this clinical trial studying?

An observational study of Non Small Cell Lung Cancer and Liquid Biopsy, run by Erasmus Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Anne-Marie Dingemans, MD, PhD (+31107040704, a.dingemans@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: 10 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05221372, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2022.

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