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Trial registered on ANZCTR


Registration number
ACTRN12616000581460
Ethics application status
Approved
Date submitted
27/04/2016
Date registered
5/05/2016
Date last updated
5/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Narrow Band Imaging (NBI) and Computed Tomography (CT) following head and neck cancer treatment.
Scientific title
Surveillance of Head and Neck Cancer patients 3-5 years post treatment using a single NBI procedure and CT chest with computer aided diagnostics.
Secondary ID [1] 289086 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Cancer 298541 0
Surveillance for second primary cancer 298542 0
Lung cancer 298543 0
Condition category
Condition code
Cancer 298625 298625 0 0
Head and neck
Cancer 298626 298626 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The first is a breathing test done in the Lung Function lab. This should take 20 minutes and you may well have had this before. This is to see whether there is any other lung conditions which can make early cancers more likely.

The second is the camera into the throat and lungs ( Bronchoscopy). When we do the camera examination you will be given medication to make you sleepy to make the procedure as comfortable as possible. This is a normal practice with many such tests. This is done as an outpatient day case procedure. The medication is given through a small needle (cannula) and a numbing medicine is sprayed in the back of the throat. The doctor first of all looks in detail at the throat region with the assistance of the ENT surgeon, then passes the scope down through the vocal cords (voice box) into the lung (air passages). This is a standard procedure. In the first part of the procedure just a standard light will be used and the appearance recorded. Then the blue light will be used to look at the same regions. This blue light has a wavelength of 450 nm- it is not a laser and does not affect the bronchial tubes in any way. Any areas which require a sample to be taken will be noted and samples taken using a biopsy (sample) forcep. This is a standard method for obtaining material to confirm whether there is anything significant which may require treatment. Biopsies of the throat region will be done with the ENT surgeon, and biopsy of the air passages by the Respiratory specialist doing the procedure. One additional biopsy of normal appearing airway lining will be taken for comparison. This is a tiny amount of material (only 1 or 2 millimeters across). This is so we can check that we are not missing significant changes elsewhere in the air passages.In the procedure approximately 10 minutes of white light is used, then approximately 10 minutes NBI blue light is used, dependent on the number of lesions and biopsies required. Patients go home the same day.

Biopsies will be followed up at an outpatient clinic the following week. Any treatment which is required will be discussed between yourself and your doctor as is the usual practice following a biopsy.

You will be therefore be participating in a cross-over study. In a cross-over study the patients have one method of investigation followed by a different method and the two are compared. In this study the first method is the white light and the second method is the blue light. We want to compare which light gives the best results in terms of finding early cancers.

This research project has been designed to make sure the researchers interpret the results in a fair and appropriate way and avoids study doctors or participants jumping to conclusions. This is done by reporting of the biopsy results by the pathologist without knowledge of which colour light was in use when the abnormality prompting the biopsy was found.

The third procedure is a CT (CAT) scan of the chest. This is also done as a day case It takes only 5 minutes and patients lie on the examination table and the scan is taken as they hold a single deep breath. Results of this will also be discussed at the time of the other appointment as above.

If the camera test and CT are negative for any abnormal areas then just normal follow-up will continue with the ENT department. If there are abnormalities of the camera depending on biopsy there may be a need for a follow-up bronchoscopy in 3-6 months time; if there is a cancer there steps will be initiated immediately to organise treatment for that. Similarly if there are abnormalities on the CT chest these may require follow-up scan in 3-6 months, or a biopsy in those few cases where there is an obvious abnormality requiring immediate attention.

The study will run for two years however only these initial 3 tests are done for the research study. Follow-up tests would only be done in the event of abnormalities as mentioned above. We would follow the results of any additional biopsies or treatments over the two years of the study. Those treatments would be directed by your own doctors who already follow your case up, or the Respiratory specialist who did the camera test.
Intervention code [1] 294596 0
Early detection / Screening
Intervention code [2] 294609 0
Diagnosis / Prognosis
Comparator / control treatment
All patients have surveillance procedure. During that procedure the CONTROL is white light inspection. The comparator is the number of biopsies when NBI is used immediately following white light. results of the comparison are detemined by the HISTOLOGY on biopsies- how many more patients with significant ( severe dysplasia or worse) lesions are found with NBI than white light.
Control group
Active

Outcomes
Primary outcome [1] 298121 0
Yield of preneoplastic lesions in the upper airway and bronchus as detected by white light bronchoscopy and NBI bronchoscopy. The outcome is measured by HISTOLOGY YIELD BY WHITE LIGHT VERSUS NBI- The important pathology is moderate dysplasia or worse up to carcinoma in situ.
Timepoint [1] 298121 0
At bronchoscopy/upper airway inspection
Primary outcome [2] 298122 0
Yield of malignant lesions by CT chest
Timepoint [2] 298122 0
At time of bronchoscopy
Secondary outcome [1] 323226 0
Correlation between yield of abnormal lesions using NBI and COPD severity. COPD assessed using the GOLD classification of lung function severity.
Yield of lesions of moderate dysplasia or worse will be expressed comparing Gold class 0-2 with Gold Class 3-4.
Timepoint [1] 323226 0
At time of bronchoscopy

Eligibility
Key inclusion criteria
Patients 3-5 years post completion of curative treatment of Head and Neck Cancer ( either surgery or chemoradiation.)
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe COPD or active coronary artery disease making bronchoscopy unsafe

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Pathologist blinded to whether biopsies taken on NBI or white light
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
NBI biopsies: Statistical analyses will be calculated for
1. All positive biopsies from moderate dysplasia up to invasive malignancy
2.Biopsies of early cancer ( severe dysplasia and carcinoma in situ)
The data will be analysed on a per-lesion basis and a per patient basis. For the per-lesion analysis, each biopsy specimen was evaluated and considered positive if the final diagnosis was positive. For the per-patient analysis, each patient was considered positive if he or she had at least one positive lesion (biopsy). The primary efficacy endpoint will be the relative sensitivity of a white light bronchoscopy (WLB)+ NBI examination as compared with a WLB examination alone for the detection of moderate/severe dysplasia, CIS, or invasive cancer. In addition, the false-positive rate (i.e., 1-specificity) will be determined. This methodology has previously been published for fluorescence bronchoscopy.

Statistically unbiased estimates of sensitivity and specificity are not possible to obtain because serial sections of the entire tracheobronchial tree would need to be examined after the bronchoscopic procedures for these to be defined, as outlined in the published studies of Herth and Lam on NBI and autofluorescence. Nevertheless, because the objective of the study is to determine whether the addition of NBI examination to WLB is better than WLB alone, the relative sensitivity, or the ratio of the sensitivity of WLB + NBI as compared with WLB alone, along with the 95% confidence interval (CI), will be calculated to evaluate the contribution of the fluorescence examination to detect neoplastic lesions. A relative sensitivity more than 1 would indicate a significant improvement of WLB + NBI versus WLB alone. Two other statistically unbiased estimates, the positive predictive value and negative predictive value, will also be calculated to evaluate the performance.

Published data on white light versus NBI in the bronchus (Herth) and in the Head and Neck ( Nguyen) reveal differences in sensitivity for INTRAEPITHELIAL NEOPlASIA ( SEVERE DYSPLASIA AND CARCINOMA IN SITU) of 18% vs 53% ( Herth) and 40% vs 96% ( Nguyen). If we use Herth’s results we estimate conservatively that there is a 30% difference in sensitivity with the use of NBI. Therefore calculating sample size for a paired t test we obtain a sample size of 90, which uses a sigma of 1.0, power of 0.8, and alpha of 0.05. (http://homepage.stat.uiowa.edu/~rlenth/Power/index.html). That is there would be 90 patients in total as each patient is their own control.
An alternative way to calculate patient numbers would be using a test of 2 proportions: Every year post curative treatment of H&N cancer 3% of patients are diagnosed with an invasive second primary aerodigestive tract tumour. By sampling at 3-5 years post the detection of significant SPM would rise from 9% to 30% using NBI for both head and neck and bronchus regions (“bringing forward” the cases that would have been found up to 10 years per published studies- that is, for the NBI group ALL cases which would have been detected each year would be found at that 5 year timepoint.). Sample size to detect a difference between 9% and 30 % would be 80 patients, with alpha value of 0.05 and Power of 0.90. (http://homepage.stat.uiowa.edu/~rlenth/Power/index.html). This is similar to the number calculated above.
Overall cancer incidence will be on the basis of NBI procedure biopsies of in situ carcinoma and invasive carcinoma as above combined with positive biopsy of cancer as a result of CT chest (either by bronchoscopic transbronchial lung biopsy or CT needle biopsy).




2. Risk of second primary lung primaries compared to degree of obstructive airways disease.
Airways obstruction is classified into quartiles as per the GOLD criteria as follows:
Gold 1 FEV 1 >80%
Gold 2 FEV 1 50-79%
Gold 3 FEV1 30-49%
Gold 4 FEV1 <30%
Yield of lesions of moderate dysplasia and worse will be calculated for each Gold class and the relative incidence in each class compared using Mann Whitney test

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2016
Actual
Date of last participant enrolment
Anticipated
1/05/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA
Recruitment hospital [1] 5687 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 5688 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 5701 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 13176 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [2] 13188 0
6150 - Murdoch
Recruitment postcode(s) [3] 13189 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 293466 0
Hospital
Name [1] 293466 0
Royal Brisbane and Womens Hospital
Country [1] 293466 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Womens Hospital
Address
Department of Thoracic Medicine
James Mayne Building
Butterfield St
Herston
Queensland 4029
Country
Australia
Secondary sponsor category [1] 292288 0
Commercial sector/Industry
Name [1] 292288 0
Olympus Australia
Address [1] 292288 0
3 Acacia Place, Notting Hill VIC 3168 Australia
Country [1] 292288 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294907 0
Royal Brisbane and Womens Hospital Human Research Ethics Committee
Ethics committee address [1] 294907 0
Ethics committee country [1] 294907 0
Australia
Date submitted for ethics approval [1] 294907 0
04/07/2015
Approval date [1] 294907 0
26/08/2015
Ethics approval number [1] 294907 0
15 QRBW-251

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65418 0
Dr David Fielding
Address 65418 0
Dept Thoracic Medicine
James Mayne Building
Royal Brisbane and Womens Hospital
Butterfield ST
Herston QLD 4029
Country 65418 0
Australia
Phone 65418 0
+61736464241
Fax 65418 0
+61736465651
Email 65418 0
[email protected]
Contact person for public queries
Name 65419 0
David Fielding
Address 65419 0
Dept Thoracic Medicine
James Mayne Building
Royal Brisbane and Womens Hospital
Butterfield ST
Herston QLD 4029
Country 65419 0
Australia
Phone 65419 0
+61736464241
Fax 65419 0
Email 65419 0
[email protected]
Contact person for scientific queries
Name 65420 0
David Fielding
Address 65420 0
Dept Thoracic Medicine
James Mayne Building
Royal Brisbane and Womens Hospital
Butterfield ST
Herston QLD 4029
Country 65420 0
Australia
Phone 65420 0
+61736464241
Fax 65420 0
Email 65420 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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