NCT04737382

Brief Summary

Initially, patients with EGFR mutation positive NSCLC respond well to osimertinib, a third generation EGFR tyrosine kinase inhibitor (TKI), but eventually progress. Upon progression multiple resistance mechanisms have been described and new therapeutic strategies are being developed to target these resistance mechanisms. Thorough and complete osimertinib resistance analysis enables optimal treatment decision making and might identify new targets for molecular treatment, thereby potentially improving patient outcome.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Aug 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

6 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 22, 2019

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

October 24, 2019

Completed
1.3 years until next milestone

First Posted

Study publicly available on registry

February 3, 2021

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 22, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 22, 2024

Completed
Last Updated

October 10, 2023

Status Verified

October 1, 2023

Enrollment Period

5 years

First QC Date

October 24, 2019

Last Update Submit

October 6, 2023

Conditions

Keywords

OsimertinibEGFR positive NSCLCResistance

Outcome Measures

Primary Outcomes (2)

  • EGFR TKI resistance analysis on tumor biopsies and ctDNA

    Complete osimertinib resistance analysis in tissue and plasma for all patients in the Netherlands that progress on osimertinib treatment

    Trough study completion, an average of 2 years

  • Recommendation for subsequent treatment

    Evaluation of these results in an MTB meeting and recommendations for subsequent treatment.

    Trough study completion, an average of 2 years

Secondary Outcomes (3)

  • Evaluate recommended and actually treatment

    Trough study completion, an average of 2 years

  • Evaluate plasma and tumor tissue

    Trough study completion, an average of 2 years

  • Evaluate success rate

    Trough study completion, an average of 2 years

Study Arms (1)

Biopsy and blood

OTHER

A histological core biopsy of a tumor lesion and a blood sample for ctDNA analysis will be collected

Diagnostic Test: biopsyDiagnostic Test: ctDAN analysis

Interventions

biopsyDIAGNOSTIC_TEST

The formalin fixed material will be processed for molecular analysis in a clinically validated diagnostic pipeline according to ISO 15189 or other acceptable standard

Biopsy and blood
ctDAN analysisDIAGNOSTIC_TEST

ctDNA analysis will be performed using the AVENIO ctDNA targeted kit according to the guidelines from the manufacturer with respect to isolation, library preparation and bioinformatics analysis.

Biopsy and blood

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed metastatic NSCLC, characterized by a sensitizing EGFR mutation.
  • \. Progressive disease, as assessed by the treating physician during osimertinib monotherapy.
  • \. Eligible for subsequent treatment. 4. Willing to undergo a histological biopsy and withdrawal of a blood sample for ctDNA analysis.
  • \. Technically possible to take a histological biopsy.

You may not qualify if:

  • \- 1. Osimertinib discontinuation before blood draw and / or histological tumor biopsy.
  • \. Initiation of a new line of anticancer therapy before blood draw and / or histological tumor biopsy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

The Netherlands Cancer Institute-Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066 CX, Netherlands

RECRUITING

Vrije Universiteit Medisch Centrum

Amsterdam, Netherlands

NOT YET RECRUITING

Universitair Medisch Centrum Groningen

Groningen, Netherlands

NOT YET RECRUITING

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

NOT YET RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, Netherlands

NOT YET RECRUITING

Erasmus MC, Universitair Medisch Centrum Rotterdam

Rotterdam, Netherlands

NOT YET RECRUITING

Related Publications (1)

  • van der Wel JWT, Ernst SM, Jebbink M, van den Broek D, Badrising SK, Steinbusch LC, Ruiter G, Theelen WSME, van Veggel BAMH, Smit J, Dingemans AM, Paats MS, Dubbink HJ, Hashemi SMS, Radonic T, Cohen D, van der Wekken AJ, Ter Elst A, Timens W, Hendriks LE, Speel EJM, Disselhorst MMJ, Welling A, van der Meer F, Bosch LJW, Monkhorst K, Boelens MC, Smit EF, de Langen AJ. Determining the optimal approach to identify osimertinib resistance; the first line osimertinib cohort of the OSIRIS study. Lung Cancer. 2025 Nov;209:108783. doi: 10.1016/j.lungcan.2025.108783. Epub 2025 Sep 28.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

CytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • J de Langen, MD, PhD

    The Netherlands Cancer Institute-Antoni van Leeuwenhoek

    PRINCIPAL INVESTIGATOR

Central Study Contacts

J de Langen, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 24, 2019

First Posted

February 3, 2021

Study Start

August 22, 2019

Primary Completion

August 22, 2024

Study Completion

August 22, 2024

Last Updated

October 10, 2023

Record last verified: 2023-10

Locations