Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients.

Lung Neoplasms Clinical Trial

— NIRVANA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03220230
• Other study ID #: X9001083
• Secondary ID: NIRVANA
• Status: Completed
• Start date: July 6, 2015
• Est. completion date: October 30, 2018

Study information

• Verified date: October 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 4240
• Est. completion date: October 30, 2018
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms

Locations

Country	Name	City	State
Brazil	Instituto Goiano de Oncología e Hematologia	Aparecida De Goiana	Goias
Brazil	Fundaçao Pio XII, Hospital do Cancer de Barretos	Barretos
Brazil	Hospital Luxemburgo	Belo Horizonte	MG
Brazil	Hospital Felicio Rocho	Belo Horizonte /MG	MG
Brazil	Liga Paranaense de Combate ao Cancer Hospital Erasto Gaetner	Curtiba-PR
Brazil	Centro Regional Integrado de Oncologia	Fortaleza	Caera
Brazil	Instituto de Cancer de Londrina	Londrina	Parana
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre
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	Hospital Santa Izabel	Salvador
Brazil	Nucleo de Oncologia da Bahia	Salvador
Brazil	Centro de Pesquisa da Universidade Federal de Sao Paulo - UNIFESP	Sao Paulo	VILA Clementino
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Paulo
Brazil	Instituto de Oncologia de Sorocaba - ONCO Clinicas Especializadas SC Ltda	Sao Paulo
Brazil	A.C. Camargo Cancer Center	São Paulo
Brazil	Hospital Israelita Albert Einstein	São Paulo/SP
Chile	Hospital Base de Arica	Arica
Chile	Hosp Regional de Concepcion	Concepcion
Chile	Universidad Católica del Norte	Coquimbo
Chile	Hospital Clinico Universidad de Chile, Seccion de Oncologia	Independencia	Santiago, RM
Chile	Hospital Base de Puerto Montt	Puerto Montt	Region DE LOS Lagos
Chile	Centro Internacional de Estudios Clinicos	Santiago	RM
Chile	Instituto Nacional Del Torax	Santiago
Chile	Instituto Clinico Oncologico del Sur (ICOS)	Temuco	Ranco
Chile	Hospital Base de Valdivia	Valdivia	Region DE LOS Lagos
Peru	Hospital Carlos Alberto Seguin Escobedo	Arequipa
Peru	Hospital Nacional Hipolito Unanue	El Agustino
Peru	Clínica Quirurgica Santa Maria	Lima
Peru	Clinica San Felipe	Lima
Peru	Hospital Central de la Fuerza Aerea Peruana	Lima
Peru	Instituto Nacional de Enfermedales Neoplasicas (INEN)	Lima
Peru	Oncosalud	Lima
Peru	Unidad de Investigacion de la Clinica Internacional - Sede San Borja	Lima
Peru	Centro de Investigación Clínica Trujillo E.I.R.L.	Trujillo

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Brazil,  Chile,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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