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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616001071415
Ethics application status
Approved
Date submitted
1/08/2016
Date registered
10/08/2016
Date last updated
10/08/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Oral Cancer Resection Guided by Narrow Band Imaging on Local Recurrence
Scientific title
Local Recurrence Rates of Oral Squamous Cell Carcinoma Resected with Narrow Band Imaging Guidance
Secondary ID [1] 289802 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MARGINS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oral Squamous Cell Carcinoma 299709 0
Condition category
Condition code
Cancer 299646 299646 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1) Resection of oral squamous cancer - guided by Narrow Band Imaging.
Device: Narrow Band Imaging (Olympus). Narrow Band Imaging (NBI) uses 2 narrow bands of light, one at 400-430nm and the second at 525-555nm.
Procedure: Margins around the tumour will be delineated with Narrow Band Imaging prior to tumour resection.
Resection of the oral cancer will proceed under General Anaesthesia as per usual practice. The peri-operative experience of the patient will not be altered by which group they are randomised to and will be no different to their experience had they undergone routine management outside of the trial.

2) Punch biopsies of tumour, NBI margin, WL margin and normal oral mucosa – guided by White Light Panendoscopy and Narrow Band Imaging.
Device: Narrow Band Imaging (Olympus), White Light Endoscope (full spectrum white light with wavelength inclusive of 400-700 nm).
Procedure: 5mm punch biopsies will be taken from the body of the tumour, the WL and NBI margins at 3, 6, 9 and 12 o’clock and normal tissue from the contralateral side of the oral cavity.


Specifics applicable to both interventions
Who: Completed by Consultant Otolarynology Head and Neck Surgeons
Timing:
- The interventions will occur sequentially, intra-operatively, under General Anaesthesia. Punch biopsies will be performed following margin delineation and prior to tumour resection.
- Those patients in the intervention arm will have a slightly increased time required for surgical margin delineation as they will undergo both WL and NBI nasendoscopy.
This said, the time taken for the procedures will not significantly alter the total time taken for the surgery. Total operative time depends on the clinical circumstance.
Mode of delivery: Face-to-face, single patient at a time.
Number of times: Intervention completed on a single occasion.
Location: Operating Theatre, Sir Charles Gairdner Hospital, Perth, Western Australia.



Intervention code [1] 295473 0
Treatment: Surgery
Intervention code [2] 295513 0
Treatment: Devices
Comparator / control treatment
1) Resection of oral squamous cancer - guided by White Light Panendoscopy (standard care).
Procedure: Margins around the tumour will be delineated with White Light prior to tumour resection.
Resection of the oral cancer will proceed under General Anaesthesia as per usual practice. The peri-operative experience of the patient will not be altered by which group they are randomised to and will be no different to their experience had they undergone routine management outside of the trial.

2) Punch biopsies of tumour, WL margin and normal oral mucosa – guided by White Light Panendoscopy.
Device: Narrow Band Imaging (Olympus), White Light Panendoscope
Procedure: 5mm punch biopsies will be taken from the body of the tumour, the WL margins at 3, 6, 9 and 12 o’clock and normal tissue from the contralateral side of the oral cavity.

Specifics applicable to both interventions
Who: Completed by Consultant Otolarynology Head and Neck Surgeons
Timing:
- The interventions will occur sequentially, intra-operatively, under General Anaesthesia. Punch biopsies will be performed following margin delineation and prior to tumour resection.
- The procedures completed under GA will not significantly alter the time taken for the surgery. Total operative time depends on the clinical circumstance.
Mode of delivery: Face-to-face, single patient at a time.
Number of times: Intervention completed on a single occasion.
Location: Operating Theatre, Sir Charles Gairdner Hospital, Perth, Western Australia.
Control group
Active

Outcomes
Primary outcome [1] 299112 0
Local recurrence of OSCC.
Measured by clinical examination and subsequent investigation should there be any clinical suspicion of recurrence.
Investigation for recurrence would proceed as per usual clinical practice. This includes imaging (CT scan, PET scan, MRI) and biopsy.
Timepoint [1] 299112 0
Measured at routine outpatient follow-up 3 and 5 years post initial surgery for Oral Squamous Cell Carcinoma.
Primary outcome [2] 299115 0
Disease free survival.
Measured by attendance/ non-attendance of participant at routine post-operative follow-up. Assessed by clinical examination, and follow-up imaging or biopsy as indicated by standard of care practices.
Should the patient not attend follow-up the medical record will be reviewed to determine whether the patient is alive or deceased.
Timepoint [2] 299115 0
Measured at routine outpatient follow-up 3 and 5 years post initial surgery for Oral Squamous Cell Carcinoma.
Secondary outcome [1] 326221 0
Presence/absence of OSCC at the surgical margin.
- Measured by histopathological assessment of cancer at margins (‘positive’ vs. ‘negative’ margin). Margins will be designated close, involved, clear as on standard histopathological assessment.
- Measured by molecular profiling (using Next generation Sequencing using both exome and transcriptome panels), comparing NBI margin to WL margin and tumour.
Timepoint [1] 326221 0
During the immediate post-operative period, over a time course of two weeks.
Secondary outcome [2] 326355 0
Cost effectiveness of NBI procedure compared to WL procedure.
Financial cost of treatment for Oral Squamous Cell Carcinoma.
Measured in dollars saved.
Assessed by review of medical records and data linkage to hospital cost records.
Timepoint [2] 326355 0
Measured at routine outpatient follow-up 3 and 5 years post initial surgery for Oral Squamous Cell Carcinoma.

Eligibility
Key inclusion criteria
Patients planned for surgical management of Oral Squamous Cell Carcinoma.
>18 years of age.
Patients able to give informed consent.

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Oral Squamous Cell Carcinoma planned for non-operative management.
<18 years of age.
Patients unable to give informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
-During the study, participants will be blinded to their group allocation. Upon the completion of 5 year follow-up (or sooner should the participant choose to withdraw from the study) participants will be advised of their group allocation.
-Pathologists/Radiologists will be blinded to participant allocation.
-Statisticians will be blinded to participant allocation.

Method of allocation concealment: Central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated permuted blocks stratified by sex and 10-year age group, on the day of surgery.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculations for the primary outcome are based on statistical power of 90% and two-sided 5% significance level using SAS Proc Power. The minimum required number per group was 55 patients to achieve difference of 20% between the intervention and control groups. Assuming also 20% loss to follow-up, a minimum of 66 patients per group will be required.
In our pilot study that has been published in Head & Neck, we have shown that there have been no recurrences in the NBI group. This equates to a decrease of OSCC recurrence rates from 20% of all those patients who have resection with WL down to 0% for those who have resection under NBI. The power calculation has been undertaken for this 20% difference.
Data will be analysed by blinded statisticians with intention-to-treat principles based on original group assignment. Important baseline covariates will be collected and assessed. Logistic regression, Kaplan-Meier curves and Cox proportional hazards models will be used to compare the treatment and control groups. Effect sizes with 95% confidence intervals will be reported.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA,VIC
Recruitment hospital [1] 6321 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 6322 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [3] 6323 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 13856 0
6009 - Nedlands
Recruitment postcode(s) [2] 13857 0
3052 - Parkville
Recruitment postcode(s) [3] 13858 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 294186 0
Hospital
Name [1] 294186 0
Sir Charles Gairdner and Osborne Park Health Care Group Research Advisory Committee
Address [1] 294186 0
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Country [1] 294186 0
Australia
Funding source category [2] 294187 0
Charities/Societies/Foundations
Name [2] 294187 0
Australian Dental Research Foundation
Address [2] 294187 0
PO Box 241, St Leonards NSW 1590
Country [2] 294187 0
Australia
Primary sponsor type
Individual
Name
Professor Camile Farah
Address
Oral Health Centre of Western Australia
The University of Western Australia,
17 Monash Ave
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 293012 0
Individual
Name [1] 293012 0
Professor Peter Friedland
Address [1] 293012 0
Otolaryngology Head Neck Skull Base Surgery
Ground Floor, E Block Outpatients Clinic
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Country [1] 293012 0
Australia
Other collaborator category [1] 279131 0
Individual
Name [1] 279131 0
Dr Katherine Pollaers
Address [1] 279131 0
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Country [1] 279131 0
Australia
Other collaborator category [2] 279132 0
Individual
Name [2] 279132 0
Dr Tim Iseli
Address [2] 279132 0
Otolaryngology Head & Neck Surgery Department
Royal Melbourne Hospital
300 Grattan Street
Parkville VIC 3050
Country [2] 279132 0
Australia
Other collaborator category [3] 279133 0
Individual
Name [3] 279133 0
A/Prof Martin Batstone
Address [3] 279133 0
Maxillofacial Unit
Royal Brisbane & Women's Hospital
Cnr Butterfield St and Bowen Bridge Rd
Herston QLD 4029
Country [3] 279133 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295589 0
Sir Charles Gairdner Group Human Research Ethics Committee
Ethics committee address [1] 295589 0
Level 2
A Block
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Ethics committee country [1] 295589 0
Date submitted for ethics approval [1] 295589 0
26/04/2016
Approval date [1] 295589 0
25/05/2016
Ethics approval number [1] 295589 0
2015-150
Ethics committee name [2] 295590 0
Human Ethics, The University of Western Australia
Ethics committee address [2] 295590 0
The University of Western Australia
M459, 35 Stirling Highway
Crawley WA 6009
Ethics committee country [2] 295590 0
Australia
Date submitted for ethics approval [2] 295590 0
09/06/2016
Approval date [2] 295590 0
10/06/2016
Ethics approval number [2] 295590 0
RA/4/1/8398

Summary
Brief summary
This study will compare resection of oral cancer guided by Narrow Band Imaging with resection guided by white light panendoscopy.

Who is it for?
Participants over eighteen years of age with oral squamous cell carcinoma planned for surgical management will be invited to participate in the study.

Study details:
Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will have Narrow Band Imaging and white light panendoscopy prior to surgery. Participants in the other group will have examination with white light panendoscopy prior to surgery, which is routine practice.

Participants will have a pre-treatment PET scan, blood sample, and MRI and a post-treatment PET scan and blood sample. All surgical specimens will be examined by a pathologist as is routine practice. The molecular profiles of resection margins will be analysed to confirm that NBI surgical resection margins are molecularly distinct from WL margins and the tumour. This information will be used to create a molecular biomarker panel for head and neck cancer.

Participants will be followed-up for up to 5 years post-treatment to determine local recurrence and disease free survival.

A prospective Health Economic Assessment to demonstrate the cost benefit of the use of NBI in oral cancer management will be undertaken.

Known and possible side effect(s) for each arm of the trial; Applicable to both arms:
- Oral squamous cell carcinoma, as well as treatments for Oral squamous cell carcinoma, have the potential to significantly affect patients’ quality of life, in particular their speech and swallowing.
- There is a direct relationship between the size of the resection/complexity of reconstruction and subsequent risks (including speech/swallowing impairment). Participants in one group will not universally have larger margins resected than participants in the other group, therefore increased risk of these treatment side-effects will not be universally applicable to participants in either group.

Trial website
Trial related presentations / publications
Public notes
Attachments [1] 980 980 0 0
Attachments [2] 981 981 0 0

Contacts
Principal investigator
Name 67862 0
Prof Camile Farah
Address 67862 0
Oral Health Centre WA and Head and Neck MDT
E Block Outpatients Clinic
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Country 67862 0
Australia
Phone 67862 0
+61 8 9346 7636
Fax 67862 0
Email 67862 0
camile.farah@uwa.edu.au
Contact person for public queries
Name 67863 0
Prof Camile Farah
Address 67863 0
Oral Health Centre WA and Head and Neck MDT
E Block Outpatients Clinic
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009


Country 67863 0
Australia
Phone 67863 0
+ 61 8 9346 7636
Fax 67863 0
Email 67863 0
camile.farah@uwa.edu.au
Contact person for scientific queries
Name 67864 0
Prof Camile Farah
Address 67864 0
Oral Health Centre WA and Head and Neck MDT
E Block Outpatients Clinic
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Country 67864 0
Australia
Phone 67864 0
+ 61 8 9346 7636
Fax 67864 0
Email 67864 0
camile.farah@uwa.edu.au

No information has been provided regarding IPD availability
Summary results
No Results