Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Canada Lymph Node Score Project: A Crossover Trial (CLNS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04342377
Recruitment Status : Completed
First Posted : April 13, 2020
Last Update Posted : July 27, 2022
Sponsor:
Collaborators:
Health Sciences Centre, Winnipeg, Manitoba
Royal Alexandra Hospital
Toronto General Hospital
Centre hospitalier de l'Université de Montréal (CHUM)
McGill University Health Centre/Research Institute of the McGill University Health Centre
Information provided by (Responsible Party):
Wael Hanna, McMaster University

Brief Summary:
Before deciding on treatment for patients with lung cancer, a critical step in the investigation is finding out whether the lymph nodes in the chest contain cancer cells. This is accomplished with a biopsy of the lymph nodes through the airway wall, known as Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. Guidelines require that every single lymph node in the chest be biopsied through a process called Systematic Sampling. However, emerging data suggests that the lymph nodes that appear benign on imaging and ultrasound do not need a biopsy. A proposed alternative to the inefficient Systematic Sampling is the simplified Selective Targeted Sampling of the lymph nodes, whereby only lymph nodes that look malignant are biopsied. This trial will evaluate the simplified Selective Targeted Sampling of lymph nodes and compare it to Systematic Sampling to see whether it is equally as effective in staging lung cancer.

Condition or disease Intervention/treatment Phase
Lung Cancer Non Small Cell Lung Cancer Non-small Cell Lung Cancer Stage I Non-small Cell Lung Cancer Stage II Diagnostic Test: Selective Targeted Sampling Diagnostic Test: Systematic Sampling Phase 3

Detailed Description:
Treatment decisions in Non-Small Lung Cancer (NSCLC) are reliant on a thorough staging process that includes imaging with Computed Tomography (CT), Positron Emission Tomography (PET) and Systematic Sampling (SS) of mediastinal lymph nodes (LNs) by Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA). Collectively, the results of these staging procedures dictate whether patients will be treated with surgery, radiation and/or chemotherapy. Current guidelines for SS through EBUS-TBNA mandate the biopsy of at least 3 mediastinal LN stations (4R, 4L and 7) in the chest, even if they appear normal on CT and PET scan. Despite improvements in diagnostic techniques and safety, LN biopsies remain onerous for the patient and costly to our healthcare system. SS is also unreliable, yielding inconclusive pathology results in 42.14% of cases, especially for Triple Normal LNs, which are LNs that appear normal on PET, and CT, and EBUS. In fact, SS results in mostly negative or inconclusive biopsies for Triple Normal LNs, which may be due in part to their very low probability (< 6%) of malignancy. As such, the researchers have proposed to replace the onerous and unreliable process of SS by a simpler Selective Targeted Sampling (STS) staging process. In STS, Triple Normal LNs will not be biopsied, due to the very high negative predictive value (NPV) of malignancy. STS follows the simple notion that only LNs that have the potential to be malignant should be biopsied, whereas LNs which are very likely benign (i.e. Triple Normal LNs) should not be biopsied.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: A prospective pan-Canadian, multicentered, non-inferiority crossover study design
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Improving Preoperative Lung Cancer Staging Through the Canada Lymph Node Project: A Pan-Canadian Multicentered Crossover Trial
Actual Study Start Date : November 30, 2020
Actual Primary Completion Date : June 30, 2022
Actual Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Selective Targeted Sampling

During patients' Endobronchial Ultrasound (EBUS) procedure, they will first undergo:

Selective Targeted Sampling - endosonographic assessment of at least 3 mediastinal lymph node stations (4R, 4L, and 7) using the four criteria of the Canada Lymph Node Score (predictor of nodal disease during Endobronchial Ultrasound). Each lymph node will be assigned a CLNS ranging from 0 to 4. Triple Normal lymph nodes will be defined as those that appear normal on CT (diameter < 1 cm), AND normal on PET (SUV < 2.5), AND normal on EBUS (CLNS < 2). Lymph nodes that are found to be Triple Normal will be marked as "Not for Biopsy", whereas all other lymph nodes will be biopsied.

Diagnostic Test: Selective Targeted Sampling
Mediastinal lymph nodes are assessed with the CLNS, and only those appearing malignant with the score are biopsied. Triple Normal lymph nodes (normal appearing on PET, CT and EBUS) are not biopsied.
Other Name: STS

Active Comparator: Systematic Sampling

Upon completion of Systematic Targeted Sampling, all patients will crossover and receive the standard of care:

Systematic Sampling - all lymph nodes previously marked as "Not for Biopsy" will be biopsied.

At the conclusion of the EBUS procedure, all nodal stations would have been sampled as is mandated by current guidelines.

Diagnostic Test: Systematic Sampling
All examined mediastinal lymph nodes are biopsied, regardless of whether they appear normal during PET, CT and EBUS.
Other Name: SS




Primary Outcome Measures :
  1. Non-Inferiority Margin between Selective Targeted Sampling and Systematic Sampling [ Time Frame: 2 years ]
    A margin of 5% or less would be considered satisfactory for STS to be deemed non-inferior to SS.


Secondary Outcome Measures :
  1. Diagnostic Statistics (between staging methods) [ Time Frame: 2 years ]
    Sensitivity, specificity, negative predictive value and positive predictive value

  2. Agreement (between staging methods) [ Time Frame: 2 years ]
    Based on Cohen's Kappa statistics

  3. Inconclusive Biopsy Rate [ Time Frame: 2 years ]
    Percentage of lymph nodes with inconclusive pathology from biopsy

  4. Diagnostic Yield (accuracy) [ Time Frame: 2 years ]
    Proportion of lymph nodes with a pathological diagnosis for both sampling methods

  5. Difference in Procedure Length [ Time Frame: 2 years ]
    For each sampling method (in minutes)

  6. Difference in Cost per Procedure [ Time Frame: 2 years ]
    For each sampling method (sum of dollar costs for EBUS procedure)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Both CT and PET scans completed prior to EBUS
  • Suspected or confirmed NSCLC requiring mediastinal staging
  • cN0-cN1 as indicated by CT and PET scans

Exclusion Criteria:

  • Patients with cN0 disease AND peripheral tumors AND tumor < 2 cm in diameter, as they do not require mediastinal staging
  • Evidence of cN2 disease or higher on CT and PET scans

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04342377


Locations
Layout table for location information
Canada, Alberta
Royal Alexandra Hospital
Edmonton, Alberta, Canada, T5H 3V9
Canada, Manitoba
Health Sciences Centre
Winnipeg, Manitoba, Canada, R3A 1R9
Canada, Ontario
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada, L8N 4A6
McMaster University
Hamilton, Ontario, Canada, L8S 4L8
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
CHUM Endoscopic Tracheo-bronchial and Oesophageal Center
Montréal, Quebec, Canada, H2L 4M1
MUHC Interventional Pulmonology Department
Montréal, Quebec, Canada, H4A 3S9
Sponsors and Collaborators
St. Joseph's Healthcare Hamilton
Health Sciences Centre, Winnipeg, Manitoba
Royal Alexandra Hospital
Toronto General Hospital
Centre hospitalier de l'Université de Montréal (CHUM)
McGill University Health Centre/Research Institute of the McGill University Health Centre
Investigators
Layout table for investigator information
Principal Investigator: Waël C Hanna, MDCM, MBA, FRCSC McMaster University
Layout table for additonal information
Responsible Party: Wael Hanna, Lead Investigator, McMaster University
ClinicalTrials.gov Identifier: NCT04342377    
Other Study ID Numbers: clns_10696
First Posted: April 13, 2020    Key Record Dates
Last Update Posted: July 27, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wael Hanna, McMaster University:
Mediastinal Staging
Nodal Disease
Endobronchial Ultrasound
Diagnostic Testing
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms