NSCLC Stage IVNCT03363139
T790M Mutation Testing in Blood by Different Methodologies
An observational study of NSCLC Stage IV, run by Spanish Lung Cancer Group at 30 sites in Spain.
Trial summary
Three laboratories will participate in the study. Each laboratory will analyze the same samples by different methodologies according to the flow indicated in figure 1. This design will allow comparing the agreement performance of different methods available for T790M identification in circulating-free DNA isolated… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- NSCLC Stage IV
- What is being tested?
- Tirosin Kinase Inhibitors
- How many people
- 72 participants
- Where
- 30 sitesSpain
- Study dates
- 1 Mar 2018to 30 Mar 2019
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: EGFR mutant non small cell lung cancer patients.
Who may be able to join
- Patients diagnosed with EGFR mutant, stage IIIB and IV non small cell lung cancer and who have progressed assessed by CT Scans according to RECIST criteria v.1.1 to first or second generation EGFR tyrosine kinase inhibitors (TKIs) (e.g. gefitinib, erlotinib, afatinib) including patients who received a chemotherapy line before TKI treatment. Samples have to be drawn before the patient starts a new treatment,
- Patients have to sign the informed consent of the study
- Patients aged ≥ 18 years.
Who cannot join
- Patients progressing to third generation EGFR TKIs (e.g. Osimertinib (TKI))
- No possibility of venipuncture.
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
Spain30 sites
Hospital Príncipe de Asturias
Alcalá de Henares, Madrid, 28805
Hospital Virgen de los Lirios
Alcoy, Alicante, 03804
H. Gen. Universitario de Alicante
Alicante
Hospital Nuestra Señora de Sonsoles
Ávila, 05004
Instituto Universitario Dexeus
Barcelona, 08028
Hospital de La Santa Creu I Sant Pau
Barcelona, 08041
Hospital Universitario de Burgos
Burgos, 09006
Hospital Universitario de Ciudad Real
Ciudad Real, 13005
Hospital General Universitario de Elche
Elche, Alicante, 03203
ICO Girona -H. Dr. Josep Trueta
Girona, 17007
Hospital Clínico San Cecilio
Granada, 18012
Complejo Hospitalario de Jaén
Jaén, 23007
Complejo Hospitalario Universitario Insular de Gran Canaria
Las Palmas de Gran Canaria, Gran Canaria, 35016
Hospital Severo Ochoa
Leganés, Madrid, 28911
Complejo Asistencial Universitario de León
León, 24071
Hospital Lucus Agustí
Lugo, 27003
H.U. Puerta de Hierro
Madrid, 28035
Hospital La Paz
Madrid, 28046
Hospital Universitario Sanchinarro
Madrid, 28050
H. Carlos Haya
Málaga, 29010
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, 30120
Hospital Central de Asturias
Oviedo, Principality of Asturias
H. Son Espases
Palma de Mallorca, Mallorca, 07014
Complejo Hospitalario de Navarra
Pamplona, Navarre, 31008
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, A Coruña, 15706
Hospital Virgen del Rocío
Seville, 41013
Hospital Clínico Universitario de Valencia
Valencia, 46010
Hospital La Fe
Valencia, 46026
H. Gen. Univ. Valencia
Valencia
Hospital Arnau de Vilanova
Valencia
About this study
Official title: "T790M Mutation Testing in Blood by Different Methodologies"_RING Project
Three laboratories will participate in the study. Each laboratory will analyze the same samples by different methodologies according to the flow indicated in figure 1. This design will allow comparing the agreement performance of different methods available for T790M identification in circulating-free DNA isolated from peripheral blood.
Read the detailed description
Three blood samples per patient will be collected once at the time of progression, assessed by CT Scans according to RECIST criteria v.1.1 and before the patients start a new treatment The blood samples (5-10 mL each) will be collected in one Cell-Free DNA BCT Streck® and 2 PTT EDTA K2 (BECTON DICKINSON) collection tubes.
All samples will be labeled properly with the patient identification number and date of extraction. These samples will be stored and distributed through the 3 participating laboratories until completion of all the analyses, according to the flowchart in Figure 1. These samples will be registered in the samples collection of the Institute of Health Carlos III Registry. These samples will be kept in each participant laboratory after the completion of the RING study and the patient will be informed of that in the patient information sheet and informed consent.
cfDNA will be extracted using as starting volume 1 ml of plasma with a Maxwell® RSC instrument (Promega), using the Maxwell® RSC cfDNA Plasma Kit (MR), as specified by the manufacturer or with a Qiasymphony instrument (Qiagen company). Additionally, for BEAMing analysis, 3 ml of plasma will be used for cfDNA isolation using the the QIAamp® Circulating Nucleic Acid Kit (Qiagen company), following the manufacturer instructions.
Circulating free DNA from peripheral blood sample is an adequate source for T790M resistance mutation testing. However, comparison across different platforms has been scarcely reported. Discordant results for EGFR biomarker testing could impact patient management.
- Conditions
- NSCLC Stage IV
- Being tested
- Tirosin Kinase Inhibitors
- 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.
Tirosin Kinase InhibitorsDrug
Also called TKI
Patients that received Tyrosin Kinase inhibitors and progressed
| Study group | Role | What they receive |
|---|---|---|
| Patients with T790M mutation | Patient who has progressed to Tyrosin Kinase inhibitors and has the mutation of the gen T790M Receives: Drug: Tirosin Kinase Inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the agreement between qualitative methodologies
To evaluate the agreement performance of different methodologies available in Spain for T790M identification in circulating-free DNA isolated from blood collected at the time of progression on a first or second generation TKI
Measured: At 12 months from the first inclusion
Secondary outcomes (2)
Cost of the different methodologies
To compare the cost of the different methodologies
Measured: At 12 months from the first inclusion
Specificity and sensitivity of each cfDNA method
To estimate the specificity and sensitivity of each cfDNA method.
Measured: At 12 months from the first inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2017
- Study start1 Mar 2018
- Primary completion15 Feb 2019
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NSCLC Stage IVStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spanish Lung Cancer Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mariano Provencio, PhD, Principal investigator, Hospital Puerta del Hierro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03363139
- Sponsor's protocol ID
- GECP 17/03_RING
- Status last verified
- Apr 2020
- First submitted
- 24 Nov 2017
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Romero A, Jantus-Lewintre E, Garcia-Pelaez B, Royuela A, Insa A, Cruz P, Collazo A, Perez Altozano J, Vidal OJ, Diz P, Cobo M, Hernandez B, Vazquez Estevez S, Benitez G, Guirado M, Majem M, Bernabe R, Ortega AL, Blasco A, Bosch-Barrera J, Jurado JM, Garcia Gonzalez J, Viteri S, Garcia Giron C, Massuti B, Lopez Martin A, Rodriguez-Festa A, Calabuig-Farinas S, Molina-Vila MA, Provencio M. Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial. Mol Oncol. 2021 Jan;15(1):43-56. doi: 10.1002/1878-0261.12832. Epub 2020 Nov 13.
PubMed 33107189
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "T790M Mutation Testing in Blood by Different Methodologies"_RING Project
- ClinicalTrials.gov ID
- NCT03363139
- Acronym / sponsor ID
- GECP 17/03_RING
- Conditions
- NSCLC Stage IV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Spanish Lung Cancer GroupUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 15 Feb 2019 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 6 Dec 2017 (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.
Three laboratories will participate in the study. Each laboratory will analyze the same samples by different methodologies according to the flow indicated in figure 1. This design will allow comparing the agreement performance of different methods available for T790M identification in circulating-free DNA isolated from peripheral blood.
Detailed description
Three blood samples per patient will be collected once at the time of progression, assessed by CT Scans according to RECIST criteria v.1.1 and before the patients start a new treatment The blood samples (5-10 mL each) will be collected in one Cell-Free DNA BCT Streck® and 2 PTT EDTA K2 (BECTON DICKINSON) collection tubes.
All samples will be labeled properly with the patient identification number and date of extraction. These samples will be stored and distributed through the 3 participating laboratories until completion of all the analyses, according to the flowchart in Figure 1. These samples will be registered in the samples collection of the Institute of Health Carlos III Registry. These samples will be kept in each participant laboratory after the completion of the RING study and the patient will be informed of that in the patient information sheet and informed consent.
cfDNA will be extracted using as starting volume 1 ml of plasma with a Maxwell® RSC instrument (Promega), using the Maxwell® RSC cfDNA Plasma Kit (MR), as specified by the manufacturer or with a Qiasymphony instrument (Qiagen company). Additionally, for BEAMing analysis, 3 ml of plasma will be used for cfDNA isolation using the the QIAamp® Circulating Nucleic Acid Kit (Qiagen company), following the manufacturer instructions.
Circulating free DNA from peripheral blood sample is an adequate source for T790M resistance mutation testing. However, comparison across different platforms has been scarcely reported. Discordant results for EGFR biomarker testing could impact patient management.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with T790M mutation | – | Drug: Tirosin Kinase InhibitorsPatient who has progressed to Tyrosin Kinase inhibitors and has the mutation of the gen T790M |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- EGFR mutant non small cell lung cancer patients.
Key inclusion criteria (3 listed)
- Patients diagnosed with EGFR mutant, stage IIIB and IV non small cell lung cancer and who have progressed assessed by CT Scans according to RECIST criteria v.1.1 to first or second generation EGFR tyrosine kinase inhibitors (TKIs) (e.g. gefitinib, erlotinib, afatinib) including patients who received a chemotherapy line before TKI treatment. Samples have to be drawn before the patient starts a new treatment,
- Patients have to sign the informed consent of the study
- Patients aged ≥ 18 years.
Key exclusion criteria (2 listed)
- Patients progressing to third generation EGFR TKIs (e.g. Osimertinib (TKI))
- No possibility of venipuncture.
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 |
|---|---|---|
| Tirosin Kinase InhibitorsAlso: TKIPatients that received Tyrosin Kinase inhibitors and progressed | Drug | Patients with T790M mutation |
Primary outcome
Assess the agreement between qualitative methodologies
Time frame: At 12 months from the first inclusion
To evaluate the agreement performance of different methodologies available in Spain for T790M identification in circulating-free DNA isolated from blood collected at the time of progression on a first or second generation TKI
2 secondary outcomes
Cost of the different methodologies
Time frame: At 12 months from the first inclusion
Specificity and sensitivity of each cfDNA method
Time frame: At 12 months from the first inclusion
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 8 Apr 2020.
- Derived from this study: PubMed 33107189Romero A, Jantus-Lewintre E, Garcia-Pelaez B, Royuela A, Insa A, Cruz P, Collazo A, Perez Altozano J, Vidal OJ, Diz P, Cobo M, Hernandez B, Vazquez Estevez S, Benitez G, Guirado M, Majem M, Bernabe R, Ortega AL, Blasco A, Bosch-Barrera J, Jurado JM, Garcia Gonzalez J, Viteri S, Garcia Giron C, Massuti B, Lopez Martin A, Rodriguez-Festa A, Calabuig-Farinas S, Molina-Vila MA, Provencio M. Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial. Mol Oncol. 2021 Jan;15(1):43-56. doi: 10.1002/1878-0261.12832. Epub 2020 Nov 13.
- Grupo Español de Cáncer de PulmónLink provided by the sponsor.
- 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.
Mariano Provencio, PhD principal investigator
Hospital Puerta del Hierro
30 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NSCLC Stage IV, run by Spanish Lung Cancer Group at 30 sites in Spain.
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 3 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: finished, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain. 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?
Assess the agreement between qualitative methodologies (time frame: At 12 months from the first inclusion). 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 NCT03363139, which also lists 1 linked publication.
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 8 Apr 2020.