NCT03220230: NIRVANA

Validation of Molecular Diagnostic Thecnologies for Lung Cancer Patients.

Completed Results posted Last updated 8 November 2019

What this trial tests

trial in Lung Neoplasms in 4,240 participants. Completed in 30 October 2018.

Timeline

6 July 2015

Primary endpoint
30 October 2018

30 October 2018

Quick facts

Lead sponsor	Pfizer
Status	Completed
Study type	OBSERVATIONAL
Enrollment	4,240
Start date	6 July 2015
Primary completion	30 October 2018
Estimated completion	30 October 2018
Sites	37 locations across Chile, Brazil, Peru

Conditions studied

• Lung Neoplasms — all drugs for Lung Neoplasms →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Lung Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker Primary · 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 a

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	45
Non-Small Cell Lung Cancer Participants	1346
Non-Small Cell Lung Cancer Participants	21
Non-Small Cell Lung Cancer Participants	38

Percentage of Concordance (Agreement) Between Ventana and NGS ALK Result Primary · 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.

Accuracy

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	95.931	94.78 – 96.84

Sensitivity

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	54.217	43.548 – 64.512

Specificity

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	98.464	97.649 – 99.007

Positive Predictive Value

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	68.182	56.17 – 78.194

Negative Predictive Value

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	97.254	96.244 – 98.003

Number of Participants With Prevalence of Anaplastic Lymphoma Kinase (ALK) Biomarker by Type of Participants Secondary · 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.

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	49
Non-Small Cell Lung Cancer Participants	34

Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Smoking (Tobacco Use) History Secondary · 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.

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	9
Non-Small Cell Lung Cancer Participants	32
Non-Small Cell Lung Cancer Participants	31
Non-Small Cell Lung Cancer Participants	11

Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Stage and Classification of Biopsy Secondary · 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.

Biopsy Stage: IA

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	2

Biopsy Stage: IB

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	3

Biopsy Stage: IIA

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	1

Biopsy Stage: IIB

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	1

Biopsy Stage: IIIA

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	7

Biopsy Stage: IIIB

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	7

Biopsy Stage: IV

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	52

Biopsy Stage: None

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	10

Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Location Secondary · 40 months

Locations were categorized as lungs, pleura, node mediastinal and others.

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	56
Non-Small Cell Lung Cancer Participants	11
Non-Small Cell Lung Cancer Participants	9
Non-Small Cell Lung Cancer Participants	7

Number of Participants With Association of Anaplastic Lymphoma Kinase (ALK) Rearrangement by Gender and Age Secondary · 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).

Gender: Male

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	28

Gender: Female

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	55

Age range: 18-30 years

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	1

Age range: 31-40 years

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	7

Age range: 41-60 years

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	37

Age range: Above 61 years

Group	Value	95% CI
Non-Small Cell Lung Cancer Participants	38

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Next Generation Sequencing Technology in Lung Cancer Diagnosis.
   Cainap C, Balacescu O, Cainap SS, Pop LA. · · 2021 · cited 62× · PMID 34571741 · DOI 10.3390/biology10090864
2. Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers.
   Garrido J, Bernal Y, González E, Blanco A, et al · · 2024 · cited 11× · PMID 39097719 · DOI 10.1186/s12885-024-12737-1
3. MET Exon 14 Skipping and Novel Actionable Variants: Diagnostic and Therapeutic Implications in Latin American Non-Small-Cell Lung Cancer Patients.
   Rivas S, Sepúlveda RV, Tapia I, Estay C, et al · · 2024 · cited 3× · PMID 39769478 · DOI 10.3390/ijms252413715