Carcinoma, Non-Small-Cell LungUNICORNNCT05421936
Osimertinib for NSCLC With Uncommon EGFR Mutations
An observational study of Carcinoma, Non-Small-Cell Lung and Genes, erbB-1, run by Sheba Medical Center at 1 site in Israel.
Trial summary
This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Genes, erbB-1
- What is being tested?
- Osimertinib
- How many people
- 100 participants
- Where
- 1 siteIsrael
- Study dates
- 27 Sep 2020to Sep 2024
- Phase
- Observational
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Advanced NSCLC with uncommon EGFR mutation
Who may be able to join
- Age ≥ 18 years
- NSCLC by histologic or cytologic diagnosis
- Stage IV or stage III not amendable to curative treatment (i.e., advanced disease)
- Uncommon mutation of EGFR (exon 20 insertion excluded)
- Treated with osimertinib for advanced disease as first TKI
- Osimertinib initiated not later than end of January 2021
Who cannot join
- Lack of any follow-up data
- Lack of consent for data collection or ethics committee approval for the waiver of informed consent (i.e. for deceased patients)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Uncommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-life Practice in First Line Setting
This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Mutations found at resistance were collected.
Read the detailed description
The epidermal growth factor receptor ( EGFR) is the most common targetable driver in non-small cell lung cancer (NSCLC). Approximately 90% of the EGFR mutations include an exon 19 deletion and a L858R point mutation at exon 21. Less common mutations include, among others, G719X in exon 18, L861Q in exon 21, exon 20 insertions, S768I in exon 20, and T790M in exon 20. Osimertinib is an EGFR TKI that has been developed as non-competitive inhibitor targeting a range of EGFR mutant molecules, currently regarded as the first-line treatment of choice to EGFR mutant (EGFRm) patients. Inhibition of the less common EGFR mutant by osimertinib has been demonstrated.
Real-world data showed lower response rate (RR) and progression free survival (PFS) in patients harboring uncommon EGFR mutations compared to the ones with common mutations treated with EGFR TKIs. Osimertinib as treatment for patients with rare mutations has been assessed in a single arm phase II study in Korea. RR was 50%, PFS was 8.2 months, mOS was not reached. Osimertinib activity in patients with uncommon mutations was assessed also in a retrospective US study, time on treatment ranged from 7.7 months to 19.3 months.
This is a multi-centric, retrospective, real-world study. Study goal is to collect high quality data regarding the efficacy of osimertinib in TKI naive NSCLC patients with uncommon EGFR mutations. The primary endpoints are progression-free survival and overall survival, from osimertinib start. Secondary endpoints would be RECIST response, adverse events, time on treatment and time to CNS progression, CNS response and mechanisms of resistance if tested.
The study includes researchers from Belgium, Denmark, Israel, Switzerland, Netherlands, Germany, France, Italy and USA. Data collection will be conducted at each participating site, following ethics approval. No patient identifying information will leave each of the participating centers. Data will be collected centrally by the lead investigators and analyzed for the entire study cohort and for subgroups if deemed appropriate.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Genes, erbB-1
- Being tested
- Osimertinib
- 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.
OsimertinibDrug
Treatment as the first EGFR-TKI
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
investigator-defined PFS
Measured: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall survival
OS
Measured: From date of osimertinib initiation until date of death from any cause, assessed up to 100 months
Secondary outcomes (6)
Overall response rate
RECIST-defined ORR
Measured: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Brain response
RANO-BM
Measured: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Adverse events on osimertinib
Adverse events on osimertinib
Measured: From date of osimertinib initiation until 30 days after the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months
Time on treatment (TOT, on osimertinib)
Time on treatment (TOT, on osimertinib)
Measured: From date of osimertinib initiation until the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months
Time to CNS progression
Time to CNS progression
Measured: From date of osimertinib initiation until the date of first documented CNS progression or censured at last follow up or at date of death from any cause, whichever came first, assessed up to 100 months
Mechanisms of resistance
Results of molecular tests done at time of progression on osimertinib (if done)
Measured: From date of osimertinib initiation until the date of molecular test performed after any documented progression, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2022
- Study start27 Sep 2020
- Primary completionSep 2024 (estimated)
- Study completionSep 2024 (estimated)
Why it stopped: Result summarized and published
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.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Jair Bar, M.D., Ph.D., Sheba Medical Center
- Investigators
- Jair Bar, MD-PhD, Principal investigator, Sheba Medical Center, Ramat Gan, IsraelAlfredo Addeo, MD, Principal investigator, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05421936
- Sponsor's protocol ID
- UNICORN_226_13
- Acronym
- UNICORN
- Status last verified
- Nov 2023
- First submitted
- 30 Mar 2022
- Last updated
- 22 Nov 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 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uncommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-life Practice in First Line Setting
- ClinicalTrials.gov ID
- NCT05421936
- Acronym / sponsor ID
- UNICORN / UNICORN_226_13
- Conditions
- Carcinoma, Non-Small-Cell Lung, Genes, erbB-1
- Study type
- Observational
- Recruitment status
- SuspendedReason stopped: Result summarized and published
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Collaborators
- AstraZeneca
- Study start
- 27 Sep 2020 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 16 Jun 2022 (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.
This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Mutations found at resistance were collected.
Detailed description
The epidermal growth factor receptor ( EGFR) is the most common targetable driver in non-small cell lung cancer (NSCLC). Approximately 90% of the EGFR mutations include an exon 19 deletion and a L858R point mutation at exon 21. Less common mutations include, among others, G719X in exon 18, L861Q in exon 21, exon 20 insertions, S768I in exon 20, and T790M in exon 20. Osimertinib is an EGFR TKI that has been developed as non-competitive inhibitor targeting a range of EGFR mutant molecules, currently regarded as the first-line treatment of choice to EGFR mutant (EGFRm) patients. Inhibition of the less common EGFR mutant by osimertinib has been demonstrated.
Real-world data showed lower response rate (RR) and progression free survival (PFS) in patients harboring uncommon EGFR mutations compared to the ones with common mutations treated with EGFR TKIs. Osimertinib as treatment for patients with rare mutations has been assessed in a single arm phase II study in Korea. RR was 50%, PFS was 8.2 months, mOS was not reached. Osimertinib activity in patients with uncommon mutations was assessed also in a retrospective US study, time on treatment ranged from 7.7 months to 19.3 months.
This is a multi-centric, retrospective, real-world study. Study goal is to collect high quality data regarding the efficacy of osimertinib in TKI naive NSCLC patients with uncommon EGFR mutations. The primary endpoints are progression-free survival and overall survival, from osimertinib start. Secondary endpoints would be RECIST response, adverse events, time on treatment and time to CNS progression, CNS response and mechanisms of resistance if tested.
The study includes researchers from Belgium, Denmark, Israel, Switzerland, Netherlands, Germany, France, Italy and USA. Data collection will be conducted at each participating site, following ethics approval. No patient identifying information will leave each of the participating centers. Data will be collected centrally by the lead investigators and analyzed for the entire study cohort and for subgroups if deemed appropriate.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Advanced NSCLC with uncommon EGFR mutation
Key inclusion criteria (6 listed)
- Age ≥ 18 years
- NSCLC by histologic or cytologic diagnosis
- Stage IV or stage III not amendable to curative treatment (i.e., advanced disease)
- Uncommon mutation of EGFR (exon 20 insertion excluded)
- Treated with osimertinib for advanced disease as first TKI
Key exclusion criteria (2 listed)
- Lack of any follow-up data
- Lack of consent for data collection or ethics committee approval for the waiver of informed consent (i.e. for deceased patients)
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 |
|---|---|---|
| OsimertinibTreatment as the first EGFR-TKI | Drug | – |
Primary outcome
Progression free survival
Time frame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
investigator-defined PFS
Overall survival
Time frame: From date of osimertinib initiation until date of death from any cause, assessed up to 100 months
OS
6 secondary outcomes
Overall response rate
Time frame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Brain response
Time frame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Adverse events on osimertinib
Time frame: From date of osimertinib initiation until 30 days after the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months
Time on treatment (TOT, on osimertinib)
Time frame: From date of osimertinib initiation until the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months
Time to CNS progression
Time frame: From date of osimertinib initiation until the date of first documented CNS progression or censured at last follow up or at date of death from any cause, whichever came first, assessed up to 100 months
Mechanisms of resistance
Time frame: From date of osimertinib initiation until the date of molecular test performed after any documented progression, assessed up to 100 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 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.
Jair Bar, MD-PhD principal investigator
Sheba Medical Center, Ramat Gan, Israel
Alfredo Addeo, MD principal investigator
University Hospital, Geneva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carcinoma, Non-Small-Cell Lung and Genes, erbB-1, run by Sheba Medical Center at 1 site in Israel.
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 6 inclusion and 2 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: paused, as of the sponsor's last update on 22 Nov 2023. 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 Israel. 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?
Results are not available in the source record.
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?
Progression free survival (time frame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months). 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?
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 22 Nov 2023.