Clinical trial NCT03220230: Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients.
Official title: NON INTERVENTIONAL MULTICENTER STUDY, FOR THE VALIDATION OF MOLECULAR DIAGNOSTIC TECHNOLOGIES IN SUBJECTS WITH NON SMALL CELL LUNG CANCER (NSCLC) PROTOCOL N° X9001083
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Neoplasms
Keywords: Next generation sequencing
Lung cancer
target therapies
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-07-18
Enrollment: 4240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Lung cancer patients.

Brief summary: This is a non-interventional multi-center with investigational sites in Chile and Brasil diagnostic study to validate novel diagnostic technologies, such as Next Generation Sequencing (NGS) from both tissue and blood compared to the current gold standard. As a non-interventional study, patients will receive the treatment indicated by their doctor independently of their participation on this study.

Many cancer cells look the same under the microscope. But as these cells are studied at the molecular level, some genetic alterations or defects that are more common to certain types of cancer are identified. In some cases, these defects are what make the cells grow and multiply abnormally.

Biomarkers are the molecular fingerprints of these genetic defects. By testing a sample of your tumor for biomarkers, doctors can learn if your cancer has one of these defects, and that may point to a specific treatment choice.

One of the genetic biomarkers that are believed to cause some cancers to grow is the ALK fusion gene. About 3% to 5% of people with NSCLC may test positive for ALK. ROS1 is a receptor found in 1 to 2% of people with this type of cancer.

The present study is designed to advance the molecular testing methodologies to identify ALK+ and ROS1+ NSCLC patients.

A positive correlation with these new technologies will mean an efficient, more accurate diagnostic test, which could impact a greater number of cancer patients around world.

Detailed description: B. Lung Cancer Non-small cell lung cancer (NSCLC) is a common cause of cancer mortality throughout the world. In 2007, there were 1.5 million new lung cancer cases diagnosed worldwide, including around 733,100 cases in the South American Region.6

Approximately 85% of lung cancer is histologically defined as non small cell and the remaining 14% as small cell. The majority of patients with NSCLC present with inoperable locally advanced (Stage IIIB) or metastatic (Stage IV) disease for which no curative treatment is yet available. In newly diagnosed patients with good performance status, platinum based doublet-combination chemotherapies are associated with a median overall survival (OS) of 7.4 to 9.9 months. 7, 8, 9, 10, 11, 12 Therefore, newer agents with novel mechanisms of action are still desperately needed for this serious life-threatening disease. 15,16

The rapid and efficient identification of key driver genes in non-small-cell lung cancer (NSCLC) is becoming increasingly important.17 Clinical screening efforts have revealed that the most common mutations in lung cancer specimens involve EGFR and KRAS, along with 10 other genes that show a prevalence of mutation in 5% or less of tumors. The ALK gene is rearranged in around 3%-5% of patients with NSCLC and has been the focus of intense basic and clinical research, suggesting that the frequency of the gene rearrangement is similar in Asian and Western patients.

ROS1 is a receptor tyrosine kinase of the insulin receptor family. Chromosomal rearrangements involving the ROS1 gene were originally described in glioblastomas, where ROS1 (chromosome 6q22) is fused to the FIG gene (chromosome 6q22 immediately adjacent to ROS1), 16 and have been shown to be transforming in transgenic mice.17 More recently, ROS1 fusions were identified as potential driver mutations in an NSCLC cell line (HCC78; SLC34A2-ROS1) and an NSCLC patient sample (CD74-ROS1). 18 These fusions led to constitutive kinase activity and were associated with sensitivity in vitro and in vivo to crizotinib. As of December 2013, 16 different variants have been found.16, 17, 18

The present study is designed to advance the molecular testing methodologies to identify ALK+ and ROS1+ NSCLC patients. Advanced next generation sequencing screening methodologies will be used to identify NSCLC patients whose tumors contain a ROS1 gene inversion or translocation or an ALK translocation.

A parallel test for ALK+ by either the Abbott ALK FISH test or the Ventana ALK IHC test is necessary to validate the NGS test in all samples. A parallel test for ROS1+ by either the Kreatech FISH test or the D4D6 ROS1 IHC test may be necessary to validate the NGS test in all samples.

Eligibility criteria: Inclusion Criteria:

* Female or male, 18 years of age or older.
* Patients with histologically or cytological proven diagnosis of NSCLC, pathologically identified as adenocarcinoma.
* Patient naïve in lung cancer treatment
* Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the study prior to enrollment.
* Patients must give consent to the research use of their archived or tumor FFPE tissue, and if available, 2 blood tubes.

Exclusion Criteria:

* Prior chemotherapy treatment.

Primary outcomes:
measure: Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker
timeFrame: 40 months
measure: Percentage of Concordance (Agreement) Between Ventana and NGS ALK Result
timeFrame: 40 months
Secondary outcomes:
measure: Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker by Type of Participants
timeFrame: 40 months
measure: Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Smoking (Tobacco Use) History
timeFrame: 40 months
measure: Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Stage and Classification of Biopsy
timeFrame: 40 months
measure: Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Location
timeFrame: 40 months
measure: Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Gender and Age
timeFrame: 40 months
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Centro Regional Integrado de Oncologia
state: Caera
city: Aparecida De Goiana
country: Brazil
facility: Instituto Goiano de Oncología e Hematologia
state: Goias
city: Belo Horizonte /MG
country: Brazil
facility: Hospital Felicio Rocho
state: MG
city: Belo Horizonte
country: Brazil
facility: Hospital Luxemburgo
state: MG
city: Londrina
country: Brazil
facility: Instituto de Cancer de Londrina
state: Parana
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisa da Universidade Federal de Sao Paulo - UNIFESP
state: VILA Clementino
city: Barretos
country: Brazil
facility: Fundaçao Pio XII, Hospital do Cancer de Barretos
city: Curtiba-PR
country: Brazil
facility: Liga Paranaense de Combate ao Cancer Hospital Erasto Gaetner
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre (ISCMPA) - Hospital Santa Rita
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Prof. Fernando Figueira - IMIP
city: Rio de Janeiro
country: Brazil
facility: Instituto COI de Pesquisa Educacao e Gestao
city: Salvador
country: Brazil
facility: Hospital Da Bahia
city: Salvador
country: Brazil
facility: Hospital Santa Izabel
city: Salvador
country: Brazil
facility: Nucleo de Oncologia da Bahia
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia de Sorocaba - ONCO Clinicas Especializadas SC Ltda
city: Sao Paulo
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
city: São Paulo/SP
country: Brazil
facility: Hospital Israelita Albert Einstein
city: São Paulo
country: Brazil
facility: A.C. Camargo Cancer Center
city: Temuco
country: Chile
facility: Instituto Clinico Oncologico del Sur (ICOS)
state: Ranco
city: Puerto Montt
country: Chile
facility: Hospital Base de Puerto Montt
state: Region DE LOS Lagos
city: Valdivia
country: Chile
facility: Hospital Base de Valdivia
state: Region DE LOS Lagos
city: Santiago
country: Chile
facility: Centro Internacional de Estudios Clinicos
state: RM
city: Independencia
country: Chile
facility: Hospital Clinico Universidad de Chile, Seccion de Oncologia
state: Santiago, RM
city: Arica
country: Chile
facility: Hospital Base de Arica
city: Concepcion
country: Chile
facility: Hosp Regional de Concepcion
city: Coquimbo
country: Chile
facility: Universidad Católica del Norte
city: Santiago
country: Chile
facility: Instituto Nacional Del Torax
city: Arequipa
country: Peru
facility: Hospital Carlos Alberto Seguin Escobedo
city: El Agustino
country: Peru
facility: Hospital Nacional Hipolito Unanue
city: Lima
country: Peru
facility: Clinica San Felipe
city: Lima
country: Peru
facility: Hospital Central de la Fuerza Aerea Peruana
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedales Neoplasicas (INEN)
city: Lima
country: Peru
facility: Oncosalud
city: Lima
country: Peru
facility: Unidad de Investigacion de la Clinica Internacional - Sede San Borja
city: Lima
country: Peru
facility: Clínica Quirurgica Santa Maria
city: Trujillo
country: Peru
facility: Centro de Investigación Clínica Trujillo E.I.R.L.
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
affiliation: CEMP Pfizer Chile
name: Ricardo Armisen, MD, PhD
role: STUDY_CHAIR
References: