Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients.
- Conditions
- Lung Neoplasms
- Registration Number
- NCT03220230
- Lead Sponsor
- Pfizer
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4240
- 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.
- Prior chemotherapy treatment.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker 40 months ALK status was measured by NGS- Oncomine focus assay (OFA) and Immuno histo chemistry (IHC) Ventana. Ventana -ALK and NGS-OFA were the assay procedures performed for ALK. The corresponding analysis of a specimen had 2 possible test results including ALK positive and ALK negative. True positives (tp) were defined as NGS-OFA and Ventana positive results, whereas false negatives (fn) were defined as NGS-OFA negative results and IHC-Ventana positive results. False positives (fp) were defined as NGS-OFA positive results and IHC-Ventana negative results. True negatives (tn) were defined as NGS-OFA and IHC Ventana negative results.
Percentage of Concordance (Agreement) Between Ventana and NGS ALK Result 40 months In this outcome measure, index of concordance with accuracy, sensitivity, specificity, positive predictive value and negative predictive value were measured. Accuracy (Acc): \[tp+tn\]/\[tp+fp+fn+tn\] \*100; Sensitivity (Ss): tp/\[tp+fn\] \*100; Specificity (Sp): tn/\[fp+tn\] \*100; Positive Predictive Value (PPV): tp/\[tp+fp\] \*100; Negative Predictive Value (NPV): tn/\[fn+tn\] \*100.
- Secondary Outcome Measures
Name Time Method Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker by Type of Participants 40 months Participants were categorized on the basis of prospective and retrospective. Prospective participants were those participants whose samples were taken after the informed consent. Retrospective participants were those participants whose samples were taken before the date of signature of the informed consent.
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Stage and Classification of Biopsy 40 months Stage was defined at time of initial diagnosis of NSCLC and participants were staged according to the guidelines set by the NCCN version 7.2015. Participant's stage was categorized as: stage 0, stage IA, stage IB, stage IIA, stage IIB, stage IIIA, stage IIIB, and stage IV. Biopsy NSCLC class was categorized as adenocarcinoma, neuroendocrine tumors, other known type of NSCLC and squamous cell carcinoma.
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Location 40 months Locations were categorized as lungs, pleura, node mediastinal and others.
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Gender and Age 40 months In this outcome measure, participants were categorized according to their gender (female/male) and different age ranges (18-30 / 31-40 / 41-60 / 60 and above).
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Smoking (Tobacco Use) History 40 months The categories of smoker (tobacco use) were as follows: Never Smoker: No smoking exposure, Current Smoker: Currently uses tobacco in either cigarette, cigar or similar method (tobacco chewers excluded), Former Smoker: Participant at one time smoked but then later quit. Smoking status unknown: Participant whose smoking status is unknown.
Trial Locations
- Locations (37)
Hospital Santa Izabel
🇧🇷Salvador, Brazil
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Caera, Brazil
Instituto Goiano de Oncología e Hematologia
🇧🇷Aparecida De Goiana, Goias, Brazil
Hospital Luxemburgo
🇧🇷Belo Horizonte, MG, Brazil
Fundaçao Pio XII, Hospital do Cancer de Barretos
🇧🇷Barretos, Brazil
Hospital Felicio Rocho
🇧🇷Belo Horizonte /MG, MG, Brazil
Instituto de Cancer de Londrina
🇧🇷Londrina, Parana, Brazil
Centro de Pesquisa da Universidade Federal de Sao Paulo - UNIFESP
🇧🇷Sao Paulo, VILA Clementino, Brazil
Hospital Sao Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
Liga Paranaense de Combate ao Cancer Hospital Erasto Gaetner
🇧🇷Curtiba-PR, Brazil
Irmandade da Santa Casa de Misericordia de Porto Alegre (ISCMPA) - Hospital Santa Rita
🇧🇷Porto Alegre, Brazil
Instituto de Medicina Integral Prof. Fernando Figueira - IMIP
🇧🇷Recife, Brazil
Instituto COI de Pesquisa Educacao e Gestao
🇧🇷Rio de Janeiro, Brazil
Hospital Da Bahia
🇧🇷Salvador, Brazil
Nucleo de Oncologia da Bahia
🇧🇷Salvador, Brazil
Instituto de Oncologia de Sorocaba - ONCO Clinicas Especializadas SC Ltda
🇧🇷Sao Paulo, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
🇧🇷Sao Paulo, Brazil
Hospital Israelita Albert Einstein
🇧🇷São Paulo/SP, Brazil
A.C. Camargo Cancer Center
🇧🇷São Paulo, Brazil
Instituto Clinico Oncologico del Sur (ICOS)
🇨🇱Temuco, Ranco, Chile
Hospital Base de Puerto Montt
🇨🇱Puerto Montt, Region DE LOS Lagos, Chile
Hospital Base de Valdivia
🇨🇱Valdivia, Region DE LOS Lagos, Chile
Centro Internacional de Estudios Clinicos
🇨🇱Santiago, RM, Chile
Hospital Base de Arica
🇨🇱Arica, Chile
Hospital Clinico Universidad de Chile, Seccion de Oncologia
🇨🇱Independencia, Santiago, RM, Chile
Hosp Regional de Concepcion
🇨🇱Concepcion, Chile
Instituto Nacional de Enfermedales Neoplasicas (INEN)
🇵🇪Lima, Peru
Oncosalud
🇵🇪Lima, Peru
Unidad de Investigacion de la Clinica Internacional - Sede San Borja
🇵🇪Lima, Peru
Clínica Quirurgica Santa Maria
🇵🇪Lima, Peru
Centro de Investigación Clínica Trujillo E.I.R.L.
🇵🇪Trujillo, Peru
Universidad Católica del Norte
🇨🇱Coquimbo, Chile
Instituto Nacional Del Torax
🇨🇱Santiago, Chile
Hospital Carlos Alberto Seguin Escobedo
🇵🇪Arequipa, Peru
Hospital Nacional Hipolito Unanue
🇵🇪El Agustino, Peru
Clinica San Felipe
🇵🇪Lima, Peru
Hospital Central de la Fuerza Aerea Peruana
🇵🇪Lima, Peru