Non Small Cell Lung CancerCLNSNCT03859349
The Canada Lymph Node Score: A Feasibility Randomized Controlled Trial
A study testing Selective Targeted Sampling and Systematic Sampling in people with Non Small Cell Lung Cancer, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
Trial summary
For patients diagnosed with early stage Non-Small Cell Lung Cancer (NSCLC) on preoperative computerized tomography (CT) and positron emission tomography (PET) scans, surgical resection is usually the preferred method of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Selective Targeted Sampling and Systematic Sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteCanada
- Study dates
- 6 May 2019to 8 Jun 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Referred to have EBUS for staging of confirmed or suspected NSCLC
- Completed both a CT and PET scans
- cN0-cN1 disease indicated on CT and PET scans
Who cannot join
- Patients with cN0 disease, peripheral tumours and tumours < 2 cm in diameter (they do not require staging)
- Evidence of cN2 disease or higher on CT and PET scan
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Routine Systematic Sampling vs. Targeted Sampling of Mediastinal Lymph Nodes Prior to Lung Cancer Treatment: A Feasibility Randomized Controlled Trial
For patients diagnosed with early stage Non-Small Cell Lung Cancer (NSCLC) on preoperative computerized tomography (CT) and positron emission tomography (PET) scans, surgical resection is usually the preferred method of treatment. However, to be eligible for surgery, current guidelines require that the cancer has not spread to the lymph nodes in the chest cavity. To evaluate these lymph nodes, the standard of care is to undergo an endobronchial ultrasound (EBUS) procedure, where all the visible lymph nodes in the chest are biopsied (sampled) with a needle. Unfortunately, these biopsies are often inconclusive, especially in patients who have no evidence of mediastinal lymph node spread on pre-operative imaging. Currently, the standard of care mandates that inconclusive biopsies should be repeated, either through another EBUS, or through more invasive procedures. Repeat inconclusive biopsies are oftentimes inconclusive as well; leading to a vicious cycle of inconclusive results, a delay in treatment, morbidity for the patient, and increased costs to the healthcare system. To circumvent this issue, the investigators have developed, validated and published a 4-point score, the Canada Lymph Node Score (CLNS), which uses four features observed during EBUS to predict whether the cancer has spread to the lymph nodes or not. Research has demonstrated that lymph nodes which appear benign on both CT and PET scan that also have a CLNS of ≤1/4 are almost certainly benign. As such, it is believed that these "triple normal" lymph do not require biopsy (or repeat biopsy).
The investigators are challenging the current standard of care in lung cancer, which mandates that all the lymph nodes in the chest need to be biopsied (i.e. Systematic Sampling) before surgery, by proposing that triple normal lymph nodes can be omitted, and only those with cancer potential should be biopsied (i.e. Targeted Sampling).To prove this hypothesis, a randomized controlled trial comparing Systematic Sampling to Targeted Sampling is required. A feasibility trial is proposed to determine whether this large-scale randomized trial will be possible.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Selective Targeted Sampling, Systematic Sampling
- Keywords
- Endobronchial Ultrasound, Diagnostic Imaging, Feasibility, Randomized Controlled Trial, Clinical N0-N1 Disease
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Selective Targeted SamplingDiagnostic test
Also called STS, CLNS
After CLNS assessment, patients with proven malignant mediastinal lymph nodes will be referred for chemoradiation and patients with proven benign mediastinal lymph nodes will undergo surgical resection as per standard of care guidelines. Final pathology from the resected specimen will be considered the gold standard for analysis of sensitivity and specificity.
Systematic SamplingDiagnostic test
Also called Routine Mediastinal Staging, SS
Following routine biopsy of lymph nodes, patients with proven malignant mediastinal lymph nodes will be referred for chemoradiation and patients with proven benign mediastinal lymph nodes will undergo surgical resection as per standard of care guidelines. Final pathology from the resected specimen will be considered the gold standard for analysis of sensitivity and specificity.
| Study group | Role | What they receive |
|---|---|---|
| Systematic Sampling | Active comparator | Patients will undergo systematic sampling of lymph node stations in the mediastinum with a minimum sampling of 3 stations: 4R, 4L and 7, as is the standard of care. Other stations may be included at the endoscopist's discretion. CLNS is not used for this arm. Receives: Diagnostic Test: Systematic Sampling |
| Selective Targeted Sampling | Experimental | Patients will first undergo endosonographic assessment of 3 mediastinal lymph node stations (i.e. 4R, 4L, and 7) using the four criteria of the CLNS. Lymph node stations that exhibit a CLNS >1/4 will be biopsied as is standard of care. Lymph node stations with CLNS ≤ 1/4 will be marked as "not requiring biopsy" but will be biopsied nevertheless, so that there is no deviation from the standard of care. Other stations may be included at the endoscopist's discretion. Receives: Diagnostic Test: Selective Targeted Sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment Rate
Minimum acceptable recruitment rate is 70%
Measured: 1 Year
Procedure Length
Calculated in minutes. Recorded for both treatment arms.
Measured: 1 Day
Diagnostic Accuracy
The proportion of patients in whom the treatment (CLNS or biopsy) yielded the same diagnosis as the pathology report out of the total number of patients that have received the treatment. Recorded for both treatment arms.
Measured: 1 Year
Secondary outcomes (5)
Prevalence of Each Possible CLNS
The CLNS has five possible scores: 0/4, 1/4, 2/4, 3/4 and 4/4. The number of lymph nodes with each score will be recorded for the Experimental Arm (Targeted Sampling).
Measured: 1 Year
Frequency of Biopsies
Number of times lymph nodes had to be sampled with a transbronchial needle per EBUS procedure. Recorded for both treatment arms.
Measured: 1 Year
Percent of Inconclusive Biopsies
Number of biopsies that provided an inconclusive diagnosis out of total number of biopsies obtained. Recorded for each treatment arm.
Measured: 1 Year
Adverse Events
Number of AEs has classified by the Ottawa TM\&M System
Measured: 1 Year
Accrual Period
Duration of time to reach sample size
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start6 May 2019
- Primary completion2 Mar 2020
- Study completion8 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All participants who provide consent for participation and who fulfil eligibility criteria will be randomized with a unique randomization sequence derived from the random permuted block design (with blocks of varying sizes) in a 1:1 ratio. Participants will randomized to either Systematic Sampling (Control) or Targeted Sampling (Experimental).
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Healthcare Hamilton
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University
- Responsible party
- Principal investigator, Wael Hanna, St. Joseph's Healthcare Hamilton
- Investigators
- Waël C Hanna, MDCM, MBA, FRCSC, Principal investigator, St. Joseph's Healthcare Hamilton / McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03859349
- Sponsor's protocol ID
- sjhhclns_5829
- Acronym
- CLNS
- Status last verified
- Jun 2020
- First submitted
- 19 Feb 2019
- Last updated
- 16 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sullivan KA, Farrokhyar F, Leontiadis GI, Patel YS, Churchill IF, Hylton DA, Xie F, Seely AJE, Spicer J, Kidane B, Turner SR, Yasufuku K, Hanna WC. Routine systematic sampling versus targeted sampling during endobronchial ultrasound: A randomized feasibility trial. J Thorac Cardiovasc Surg. 2022 Jul;164(1):254-261.e1. doi: 10.1016/j.jtcvs.2021.11.062. Epub 2021 Dec 4.
PubMed 35031139
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Routine Systematic Sampling vs. Targeted Sampling of Mediastinal Lymph Nodes Prior to Lung Cancer Treatment: A Feasibility Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03859349
- Acronym / sponsor ID
- CLNS / sjhhclns_5829
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Endobronchial Ultrasound, Diagnostic Imaging, Feasibility, Randomized Controlled Trial, Clinical N0-N1 Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- St. Joseph's Healthcare HamiltonUniversity, hospital or other
- Collaborators
- McMaster University
- Study start
- 6 May 2019 (actual)
- Primary completion
- 2 Mar 2020 (actual)
- Study completion
- 8 Jun 2020 (actual)
- First posted
- 1 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For patients diagnosed with early stage Non-Small Cell Lung Cancer (NSCLC) on preoperative computerized tomography (CT) and positron emission tomography (PET) scans, surgical resection is usually the preferred method of treatment. However, to be eligible for surgery, current guidelines require that the cancer has not spread to the lymph nodes in the chest cavity. To evaluate these lymph nodes, the standard of care is to undergo an endobronchial ultrasound (EBUS) procedure, where all the visible lymph nodes in the chest are biopsied (sampled) with a needle. Unfortunately, these biopsies are often inconclusive, especially in patients who have no evidence of mediastinal lymph node spread on pre-operative imaging. Currently, the standard of care mandates that inconclusive biopsies should be repeated, either through another EBUS, or through more invasive procedures. Repeat inconclusive biopsies are oftentimes inconclusive as well; leading to a vicious cycle of inconclusive results, a delay in treatment, morbidity for the patient, and increased costs to the healthcare system. To circumvent this issue, the investigators have developed, validated and published a 4-point score, the Canada Lymph Node Score (CLNS), which uses four features observed during EBUS to predict whether the cancer has spread to the lymph nodes or not. Research has demonstrated that lymph nodes which appear benign on both CT and PET scan that also have a CLNS of ≤1/4 are almost certainly benign. As such, it is believed that these "triple normal" lymph do not require biopsy (or repeat biopsy).
The investigators are challenging the current standard of care in lung cancer, which mandates that all the lymph nodes in the chest need to be biopsied (i.e. Systematic Sampling) before surgery, by proposing that triple normal lymph nodes can be omitted, and only those with cancer potential should be biopsied (i.e. Targeted Sampling).To prove this hypothesis, a randomized controlled trial comparing Systematic Sampling to Targeted Sampling is required. A feasibility trial is proposed to determine whether this large-scale randomized trial will be possible.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- All participants who provide consent for participation and who fulfil eligibility criteria will be randomized with a unique randomization sequence derived from the random permuted block design (with blocks of varying sizes) in a 1:1 ratio. Participants will randomized to either Systematic Sampling (Control) or Targeted Sampling (Experimental).
| Arm | Type | Receives |
|---|---|---|
| Systematic Sampling | Active comparator | Diagnostic Test: Systematic SamplingPatients will undergo systematic sampling of lymph node stations in the mediastinum with a minimum sampling of 3 stations: 4R, 4L and 7, as is the standard of care. Other stations may be included at the endoscopist's discretion. CLNS is not used for this arm. |
| Selective Targeted Sampling | Experimental | Diagnostic Test: Selective Targeted SamplingPatients will first undergo endosonographic assessment of 3 mediastinal lymph node stations (i.e. 4R, 4L, and 7) using the four criteria of the CLNS. Lymph node stations that exhibit a CLNS >1/4 will be biopsied as is standard of care. Lymph node stations with CLNS ≤ 1/4 will be marked as "not requiring biopsy" but will be biopsied nevertheless, so that there is no deviation from the standard of care. Other stations may be included at the endoscopist's discretion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Referred to have EBUS for staging of confirmed or suspected NSCLC
- Completed both a CT and PET scans
- cN0-cN1 disease indicated on CT and PET scans
Key exclusion criteria (2 listed)
- Patients with cN0 disease, peripheral tumours and tumours < 2 cm in diameter (they do not require staging)
- Evidence of cN2 disease or higher on CT and PET scan
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selective Targeted SamplingAlso: STS, CLNSAfter CLNS assessment, patients with proven malignant mediastinal lymph nodes will be referred for chemoradiation and patients with proven benign mediastinal lymph nodes will undergo surgical resection as per standard of care guidelines. Final pathology from the resected specimen will be considered the gold standard for analysis of sensitivity and specificity. | Diagnostic test | Selective Targeted Sampling |
| Systematic SamplingAlso: Routine Mediastinal Staging, SSFollowing routine biopsy of lymph nodes, patients with proven malignant mediastinal lymph nodes will be referred for chemoradiation and patients with proven benign mediastinal lymph nodes will undergo surgical resection as per standard of care guidelines. Final pathology from the resected specimen will be considered the gold standard for analysis of sensitivity and specificity. | Diagnostic test | Systematic Sampling |
Primary outcome
Recruitment Rate
Time frame: 1 Year
Minimum acceptable recruitment rate is 70%
Procedure Length
Time frame: 1 Day
Calculated in minutes. Recorded for both treatment arms.
Diagnostic Accuracy
Time frame: 1 Year
The proportion of patients in whom the treatment (CLNS or biopsy) yielded the same diagnosis as the pathology report out of the total number of patients that have received the treatment. Recorded for both treatment arms.
5 secondary outcomes
Prevalence of Each Possible CLNS
Time frame: 1 Year
Frequency of Biopsies
Time frame: 1 Year
Percent of Inconclusive Biopsies
Time frame: 1 Year
Adverse Events
Time frame: 1 Year
Accrual Period
Time frame: 1 Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Derived from this study: PubMed 35031139Sullivan KA, Farrokhyar F, Leontiadis GI, Patel YS, Churchill IF, Hylton DA, Xie F, Seely AJE, Spicer J, Kidane B, Turner SR, Yasufuku K, Hanna WC. Routine systematic sampling versus targeted sampling during endobronchial ultrasound: A randomized feasibility trial. J Thorac Cardiovasc Surg. 2022 Jul;164(1):254-261.e1. doi: 10.1016/j.jtcvs.2021.11.062. Epub 2021 Dec 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Waël C Hanna, MDCM, MBA, FRCSC principal investigator
St. Joseph's Healthcare Hamilton / McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Selective Targeted Sampling and Systematic Sampling in people with Non Small Cell Lung Cancer, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment Rate (time frame: 1 Year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03859349, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.