Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients. (NIRVANA)

NON INTERVENTIONAL MULTICENTER STUDY, FOR THE VALIDATION OF MOLECULAR DIAGNOSTIC TECHNOLOGIES IN SUBJECTS WITH NON SMALL CELL LUNG CANCER (NSCLC) PROTOCOL N° X9001083

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.

Study Overview

• Status: Completed
• Conditions: Lung Neoplasms

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.

• Study Type: Observational
• Enrollment (Actual): 4240

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil
    • Fundaçao Pio XII, Hospital do Cancer de Barretos
  • Curtiba-PR, Brazil
    • Liga Paranaense de Combate ao Cancer Hospital Erasto Gaetner
  • Porto Alegre, Brazil
    • Hospital Sao Lucas Da Pucrs
  • Porto Alegre, Brazil
    • Irmandade da Santa Casa de Misericordia de Porto Alegre (ISCMPA) - Hospital Santa Rita
  • Recife, Brazil
    • Instituto de Medicina Integral Prof. Fernando Figueira - Imip
  • Rio de Janeiro, Brazil, 22793-080
    • Instituto COI de Pesquisa Educação e Gestão
  • Salvador, Brazil
    • Núcleo de Oncologia da Bahia
  • Salvador, Brazil
    • Hospital Santa Izabel
  • Salvador, Brazil, 41820-011
    • Hospital Da Bahia
  • Sao Paulo, Brazil, 18035-300
    • Instituto de Oncologia de Sorocaba - ONCO Clinicas Especializadas SC Ltda
  • Sao Paulo, Brazil
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • São Paulo, Brazil
    • A.C. Camargo Câncer Center
  • São Paulo/SP, Brazil, 05651-901
    • Hospital Israelita Albert Einstein
  • Caera
    • Fortaleza, Caera, Brazil, 60336-550
      • Centro Regional Integrado de Oncologia
  • Goias
    • Aparecida De Goiana, Goias, Brazil, 74915-520
      • Instituto Goiano de Oncologia e Hematologia
  • MG
    • Belo Horizonte, MG, Brazil, 30380-472
      • Hospital Luxemburgo
    • Belo Horizonte /MG, MG, Brazil, 30110-934
      • Hospital Felicio Rocho
  • Parana
    • Londrina, Parana, Brazil
      • Instituto de Câncer de Londrina
  • VILA Clementino
    • Sao Paulo, VILA Clementino, Brazil, 04024-002
      • Centro de Pesquisa da Universidade Federal de Sao Paulo - UNIFESP
• Chile
  • Arica, Chile
    • Hospital Base de Arica
  • Concepcion, Chile
    • Hosp Regional de Concepcion
  • Coquimbo, Chile
    • Universidad Católica del Norte
  • Santiago, Chile
    • Instituto Nacional del tórax
  • RM
    • Santiago, RM, Chile, 8420383
      • Centro Internacional de Estudios Clinicos
  • Ranco
    • Temuco, Ranco, Chile, 4810469
      • Instituto Clinico Oncologico del Sur (ICOS)
  • Region DE LOS Lagos
    • Puerto Montt, Region DE LOS Lagos, Chile, 5506667
      • Hospital Base de Puerto Montt
    • Valdivia, Region DE LOS Lagos, Chile, 5090145
      • Hospital Base de Valdivia
  • Santiago, RM
    • Independencia, Santiago, RM, Chile, 8380456
      • Hospital Clinico Universidad de Chile, Seccion de Oncologia
• Peru
  • Arequipa, Peru
    • Hospital Carlos Alberto Seguin Escobedo
  • El Agustino, Peru
    • Hospital Nacional Hipólito Unanue
  • Lima, Peru, 11
    • Clinica San Felipe
  • Lima, Peru, 41
    • Oncosalud
  • Lima, Peru, 18
    • Hospital Central de la Fuerza Aerea Peruana
  • Lima, Peru, 34
    • Instituto Nacional de Enfermedales Neoplasicas (INEN)
  • Lima, Peru, 41
    • Unidad de Investigacion de la Clinica Internacional - Sede San Borja
  • Lima, Peru
    • Clínica Quirurgica Santa Maria
  • Trujillo, Peru, 13001
    • Centro de Investigacion Clinica Trujillo E.I.R.L.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Lung cancer patients.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker	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.	40 months
Percentage of Concordance (Agreement) Between Ventana and NGS ALK Result	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.	40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker by Type of Participants	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.	40 months
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Smoking (Tobacco Use) History	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.	40 months
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Stage and Classification of Biopsy	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.	40 months
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Location	Locations were categorized as lungs, pleura, node mediastinal and others.	40 months
Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Gender and Age	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).	40 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Chair: Ricardo Armisen, MD, PhD, CEMP Pfizer Chile

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2015
• Primary Completion (Actual): October 30, 2018
• Study Completion (Actual): October 30, 2018

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 14, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): November 8, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Lung cancer; Next generation sequencing; target therapies
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: X9001083; NIRVANA (Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No