Carcinoma, Non-Small-Cell LungTATINNCT04148066
ctDNA Guided Treatment of Early Resistance to Targeted Treatment
A study testing ctDNA blood sample in people with Carcinoma, Non-Small-Cell Lung, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
Trial summary
The current strategy is to test for treatment resistance at the time of radiological progression and design subsequent treatment based on the mechanism of resistance. However, upon disease progression patients tend to deteriorate quickly and 30% - 40% of patients will not be in the clinical condition to receive next… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- ctDNA blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 2 sitesNetherlands
- Study dates
- 17 Jul 2019to 17 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
Who may be able to join
- Histologically confirmed metastatic NSCLC, characterized by a sensitizing exon 19 deletion or exon 21 L858R EGFR mutation.
- WHO performance status 0-2.
- Eligible for osimertinib treatment according to the label and according to the treating physician.
- Patients must be ≥18 years of age.
Who cannot join
- 1. Patients with symptomatic central nervous system metastases who are neurologically unstable. Unstable brain metastases except for those who have completed definitive therapy and have had a stable neurological status for 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks prior to the start of study treatment and are clinically asymptomatic.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
The Netherlands Cancer Institute-Antoni van Leeuwenhoek
Amsterdam, North Holland, 1066 CX
Erasmus MC, Universitair Medisch Centrum Rotterdam
Rotterdam
About this study
Official title: Track and Treat in NSCLC (TATIN) - ctDNA Guided Treatment of Early Resistance to Targeted Treatment in Patients With EGFR Positive NSCLC
The current strategy is to test for treatment resistance at the time of radiological progression and design subsequent treatment based on the mechanism of resistance. However, upon disease progression patients tend to deteriorate quickly and 30% - 40% of patients will not be in the clinical condition to receive next line treatment. Therefore, there is a potential for early resistance identification and directing treatment against it in order to improve patient outcome.
Read the detailed description
Next Generation Sequence (NGS) technology rapidly evolves and it is now feasible to use circulating tumor DNA (ctDNA) as a BioSource for comprehensive analysis of the molecular make up of tumors. ctDNA based techniques are able to detect the emergence of drug resistance mechanisms with high sensitivity and prior to radiological progression (12-14). This technique might identify drug resistant clones before subclonal resistance (resistance of the new clone to targeted treatment) develops and allow to eliminate the new clone with short-term additional treatment, while continuing treatment of the main oncogenic driver (EGFR exon 19 del / exon 21 L858R) with the EGFR TKI. Continuous ctDNA based monitoring will reveal the success of the additional treatment and in case the follow-up ctDNA sample shows elimination of the EGFR TKI resistant clone, the add-on treatment will be discontinued. Continuous ctDNA based monitoring might identify a new resistant clone at a later point in time and temporary treatment of this clone can be initiated. The EGFR TKI will remain the backbone of therapy and will not be discontinued (see treatment strategy 1 in Figure 3).
This continuous track and treat strategy could potentially lead to a better outcome. In this study the investigators will track all known EGFR TKI resistance mechanisms over time and select one (MET amplification) for the track and treat strategy.
Treatment strategy 1: Track and treat strategy. ctDNA based resistance monitoring. As soon as a resistant clone is detected with ctDNA, treatment will be added to the EGFR TKI. ctDNA will be continuously screened for resistant clones. Upon disappearance of the resistant clone, add-on treatment will be discontinued, while the EGFR TKI will be continued at any time. Multiple resistance mechanisms can be treated serially.
Treatment strategy 2: routine care. Treatment with an EGFR TKI will be continued until radiological progression.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- ctDNA blood sample
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ctDNA blood sampleDiagnostic test
every six weeks during treatment and upon radiological progression blood will be drawn to analyse ctDNA with Avenio ctDNA (Expanded panel) to detect all known EGFR TKI resistance mechanisms.
| Study group | Role | What they receive |
|---|---|---|
| Osimertinib and Crizotinib | Other | Osimertinib will be administered according to label: 80 mg once daily.
Crizotinib will only be prescribed upon detection of MET amplification using ctDNA. Crizotinib will be administered according to label: 250 mg bi-daily. Receives: Diagnostic Test: ctDNA blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
percentage of patients in which a drug resistant clone can be detected with ctDNA
To identify the percentage of patients in which a drug resistant clone can be detected with ctDNA before the emergence of radiological progression.
Measured: Trough study completion, an average of 2 years
Secondary outcomes (1)
the success rate of crizotinib and osimertinib combination treatment to eliminate MET amplification
To determine the success rate of crizotinib and osimertinib combination treatment to eliminate MET amplification, defined by disappearance of the MET amplification clone in a subsequent ctDNA sample.
Measured: Trough study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2019
- Study start17 Jul 2019
- Primary completion17 Dec 2021
- Study completion17 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- J de Langen, MD, PhD, Principal investigator, The Netherlands Cancer Institute-Antoni van Leeuwenhoek
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04148066
- Sponsor's protocol ID
- M18TAT
- Acronym
- TATIN
- Status last verified
- Oct 2023
- First submitted
- 30 Oct 2019
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Track and Treat in NSCLC (TATIN) - ctDNA Guided Treatment of Early Resistance to Targeted Treatment in Patients With EGFR Positive NSCLC
- ClinicalTrials.gov ID
- NCT04148066
- Acronym / sponsor ID
- TATIN / M18TAT
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 17 Dec 2021 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 1 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current strategy is to test for treatment resistance at the time of radiological progression and design subsequent treatment based on the mechanism of resistance. However, upon disease progression patients tend to deteriorate quickly and 30% - 40% of patients will not be in the clinical condition to receive next line treatment. Therefore, there is a potential for early resistance identification and directing treatment against it in order to improve patient outcome.
Detailed description
Next Generation Sequence (NGS) technology rapidly evolves and it is now feasible to use circulating tumor DNA (ctDNA) as a BioSource for comprehensive analysis of the molecular make up of tumors. ctDNA based techniques are able to detect the emergence of drug resistance mechanisms with high sensitivity and prior to radiological progression (12-14). This technique might identify drug resistant clones before subclonal resistance (resistance of the new clone to targeted treatment) develops and allow to eliminate the new clone with short-term additional treatment, while continuing treatment of the main oncogenic driver (EGFR exon 19 del / exon 21 L858R) with the EGFR TKI. Continuous ctDNA based monitoring will reveal the success of the additional treatment and in case the follow-up ctDNA sample shows elimination of the EGFR TKI resistant clone, the add-on treatment will be discontinued. Continuous ctDNA based monitoring might identify a new resistant clone at a later point in time and temporary treatment of this clone can be initiated. The EGFR TKI will remain the backbone of therapy and will not be discontinued (see treatment strategy 1 in Figure 3).
This continuous track and treat strategy could potentially lead to a better outcome. In this study the investigators will track all known EGFR TKI resistance mechanisms over time and select one (MET amplification) for the track and treat strategy.
Treatment strategy 1: Track and treat strategy. ctDNA based resistance monitoring. As soon as a resistant clone is detected with ctDNA, treatment will be added to the EGFR TKI. ctDNA will be continuously screened for resistant clones. Upon disappearance of the resistant clone, add-on treatment will be discontinued, while the EGFR TKI will be continued at any time. Multiple resistance mechanisms can be treated serially.
Treatment strategy 2: routine care. Treatment with an EGFR TKI will be continued until radiological progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Osimertinib and Crizotinib | Other | Diagnostic Test: ctDNA blood sampleOsimertinib will be administered according to label: 80 mg once daily. Crizotinib will only be prescribed upon detection of MET amplification using ctDNA. Crizotinib will be administered according to label: 250 mg bi-daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed metastatic NSCLC, characterized by a sensitizing exon 19 deletion or exon 21 L858R EGFR mutation.
- WHO performance status 0-2.
- Eligible for osimertinib treatment according to the label and according to the treating physician.
- Patients must be ≥18 years of age.
Key exclusion criteria (1 listed)
- 1. Patients with symptomatic central nervous system metastases who are neurologically unstable. Unstable brain metastases except for those who have completed definitive therapy and have had a stable neurological status for 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks prior to the start of study treatment and are clinically asymptomatic.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ctDNA blood sampleevery six weeks during treatment and upon radiological progression blood will be drawn to analyse ctDNA with Avenio ctDNA (Expanded panel) to detect all known EGFR TKI resistance mechanisms. | Diagnostic test | Osimertinib and Crizotinib |
Primary outcome
percentage of patients in which a drug resistant clone can be detected with ctDNA
Time frame: Trough study completion, an average of 2 years
To identify the percentage of patients in which a drug resistant clone can be detected with ctDNA before the emergence of radiological progression.
1 secondary outcome
the success rate of crizotinib and osimertinib combination treatment to eliminate MET amplification
Time frame: Trough study completion, an average of 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J de Langen, MD, PhD principal investigator
The Netherlands Cancer Institute-Antoni van Leeuwenhoek
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ctDNA blood sample in people with Carcinoma, Non-Small-Cell Lung, run by The Netherlands Cancer Institute at 2 sites 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: finished, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
percentage of patients in which a drug resistant clone can be detected with ctDNA (time frame: Trough study completion, an average of 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Oct 2023.