Clinical trial NCT03363139: T790M Mutation Testing in Blood by Different Methodologies
Official title: "T790M Mutation Testing in Blood by Different Methodologies"_RING Project
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: NSCLC Stage IV
Lead sponsor: Spanish Lung Cancer Group
Sponsor class: OTHER
First posted: 2017-12-06
Enrollment: 72
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: EGFR mutant non small cell lung cancer patients.

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Patients progressing to third generation EGFR TKIs (e.g. Osimertinib (TKI))
* No possibility of venipuncture.

Primary outcomes:
measure: Assess the agreement between qualitative methodologies
timeFrame: At 12 months from the first inclusion
Secondary outcomes:
measure: Cost of the different methodologies
timeFrame: At 12 months from the first inclusion
measure: Specificity and sensitivity of each cfDNA method
timeFrame: At 12 months from the first inclusion
Other outcomes:
measure: Turnaround time of different methodologies
timeFrame: At 12 months from the first inclusion
measure: Ease of use of different methodologies
timeFrame: At 12 months from the first inclusion
Locations:
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
state: A Coruña
city: Alcoy
country: Spain
facility: Hospital Virgen de los Lirios
state: Alicante
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular de Gran Canaria
state: Gran Canaria
city: Alcalá De Henares
country: Spain
facility: Hospital Príncipe de Asturias
state: Madrid
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
state: Madrid
city: Palma de Mallorca
country: Spain
facility: H. Son Espases
state: Mallorca
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Alicante
country: Spain
facility: H. Gen. Universitario de Alicante
city: Barcelona
country: Spain
facility: Instituto Universitario Dexeus
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Ciudad Real
country: Spain
facility: Hospital Universitario de Ciudad Real
city: Girona
country: Spain
facility: ICO Girona -H. Dr. Josep Trueta
city: Granada
country: Spain
facility: Hospital Clínico San Cecilio
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: León
country: Spain
facility: Complejo Asistencial Universitario de León
city: Lugo
country: Spain
facility: Hospital Lucus Agustí
city: Madrid
country: Spain
facility: H.U. Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Sanchinarro
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Málaga
country: Spain
facility: H. Carlos Haya
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valencia
country: Spain
facility: H. Gen. Univ. Valencia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Ávila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
Study officials:
affiliation: Hospital Puerta del Hierro
name: Mariano Provencio, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.