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Trial registered on ANZCTR


Registration number
ACTRN12616000715471
Ethics application status
Approved
Date submitted
24/05/2016
Date registered
30/05/2016
Date last updated
13/04/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Molecular markers to delineate excision margins in head and neck squamous cell cancer - a bilateral prospective study in Australia and India
Scientific title
Analysis of surgical margins with molecular markers, p53 and eIF4E to investigate the recurrence and prognosis in patients with head and neck squamous cell carcinoma at Royal Darwin Hospital, Northern Territory and Christian Medical College and Hospital Vellore, India - a prospective study
Secondary ID [1] 289247 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and neck squamous cell carcinoma 298823 0
Condition category
Condition code
Cancer 298882 298882 0 0
Head and neck

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
As part of the routine management patients diagnosed with mucosal head and neck squamous cell carcinoma undergo wide local excision. The surgical margins are identified and labeled by the surgeon before the biopsy specimens are sent for routine histopathological analysis. The specimens that are reported to have all the margins free of tumour are enrolled in the study for Immunohistochemical analysis. The tumour free mucosal margins undergo further immunostaining with p53 and eIF4E. This study only involves the immunohistochemistry analysis using p53 and eIF4E.
The follow up period for each participant is minimum of 12 months for disease recurrence /progression
Intervention code [1] 294788 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298348 0
To assess
how many of the surgical margins free of tumour with routine Haematoxylin and Eosin show positivity with p53 and/or eIF4E ( by Immunohistochemistry)

Timepoint [1] 298348 0
Tests to be done after the surgical margins are reported free of tumour on routine Haematoxylin and Eosin staining
Primary outcome [2] 298438 0
how many of the patients with positive p53 and /or e IF4E surgical margins have recurrence of tumour or metastasis during their follow up visits.
This will be assessed by review of medical records for clinical outcomes
Timepoint [2] 298438 0
The follow up review visits are scheduled until minimum of 12 months post surgery
Secondary outcome [1] 323910 0
Can the recurrence of disease be correlated to positivity with p53 and e IF4E
This will be assessed by local examination, biopsy of a suspicious lesion, MRI scans and doing statistical analysis on the data collected
Timepoint [1] 323910 0
how soon post excision of tumour has the tumour recurred - 2, 3, 6 months
Secondary outcome [2] 324239 0
Can the progression of disease be correlated to positivity with p53 and e IF4E
This will be assessed by local examination, biopsy of a suspicious lesions, MRI scans and doing statistical analysis on the data collected
Timepoint [2] 324239 0
how soon post excision of tumour has the tumour spread and metastasized - 2, 3, 6 months

Eligibility
Key inclusion criteria
All patients diagnosed with mucosal head and neck squamous cell carcinoma with negative surgical margins on histopathology at the Royal Darwin Hospital and Christian Medical College Vellore
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients diagnosed with any other histological type of mucosal head and neck cancers, and whose primary modality of therapy was surgery.
*Patients whose surgical margins showed dysplasia, carcinoma – in – situ, tumour and was less than 5mm distant from invasive tumour on histopathological examination
*Patients with metastatic disease except a single regional lymph node with no extracapsular spread
*Patients with multiple foci of peri-neural invasion
Patients with lymphovascular invasion
*Patients with previous radiotherapy and chemotherapy
*Patients in whom the margins cannot be defined or with an unknown primary
*Patients under 18 years of age
*Patients who are pregnant

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size- The average number of patients at Darwin and Vellore are 20 and 70 per year respectively. Most patients present late and obtaining a tumour free margin is a challenge. We anticipate performing IHC on 30 to 40 patients.
The data on the surgical margins will be analysed statistically with SPSS software. Contingency table and the X2 test will be used to evaluate the association of e IF4E and p53 in the surgical margins with race, sex, stage, lymph node status, histological grade, post-operative radiation and e IF4E and p53 expression in the tumour and margins. A univariate analysis of clinical factors will be performed using Cox model to identify those variables significantly associated with prognosis. Multivariate analysis will be performed to test for simultaneous effect of two or more factors. Event –time distributions for recurrence will be estimated by Kaplan- Meier method and compared by the log rank test to determine the individual and combined effect of e IF4E and p53 expression in the margins. Similar curves will be performed to determine the effect of nodal status with e IF4E and p53 levels in the margins as nodal status is a significant prognostic factor in HNSCCs.
The consistency of protocol at both the sites will be assessed and the study will be periodically reviewed.

Recruitment
Recruitment status
Completed
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)
NT
Recruitment hospital [1] 5812 0
Royal Darwin Hospital - Tiwi
Recruitment outside Australia
Country [1] 7885 0
India
State/province [1] 7885 0
Tamil Nadu

Funding & Sponsors
Funding source category [1] 293626 0
University
Name [1] 293626 0
Charles Darwin University
Address [1] 293626 0
Charles Darwin University
Ellengowan Drive,
PO Box 40146
Casuarina
Darwin
Northern Territory 0811
Country [1] 293626 0
Australia
Primary sponsor type
Individual
Name
Rama Jayaraj
Address
Faculty of Engineering, Health, Science and the Environment
CHARLES DARWIN UNIVERSITY
Ellengowan Drive,
Casuarina
Darwin 0909
Northern Territory
AUSTRALIA

Country
Australia
Secondary sponsor category [1] 292458 0
Individual
Name [1] 292458 0
Mahiban Thomas
Address [1] 292458 0
Department of Maxillofacial surgery
Royal Darwin Hospital
105 Rocklands Drive,
Tiwi
Darwin
NT 0810

Country [1] 292458 0
Australia
Other collaborator category [1] 278997 0
Hospital
Name [1] 278997 0
Christian Medical College and Hospital
Address [1] 278997 0
Norman Pathology,
IDA Scudder Rd,
Vellore,
Tamil Nadu 632004,
India

Country [1] 278997 0
India

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295063 0
Human Reseach Ethics Committee of the Northern Territory
Ethics committee address [1] 295063 0
Menzies school of health Research
John Mathews Building
Building 58
Royal Darwin Hospital Campus
Rocklands Drive,
Tiwi
Darwin
NT 0810
Ethics committee country [1] 295063 0
Australia
Date submitted for ethics approval [1] 295063 0
10/05/2013
Approval date [1] 295063 0
12/11/2013
Ethics approval number [1] 295063 0
HREC 13- 2036
Ethics committee name [2] 295064 0
Institustional Review Board Christian Medical College Vellore
Ethics committee address [2] 295064 0
Bagayam
Thorapadi,
Vellore
Tamil Nadu 632002
Ethics committee country [2] 295064 0
India
Date submitted for ethics approval [2] 295064 0
30/06/2014
Approval date [2] 295064 0
04/09/2014
Ethics approval number [2] 295064 0
IRB Min. No. 8967

Summary
Brief summary
The primary purpose of this study is to evaluate whether the presence of two antibodies, eIF4E and p53, in samples of tissue from the edge of surgically removed tumours in the head and neck may correspond with cancer progression and recurrence.
Who is it for?
You may be eligible to participate in this study if you are aged 18 or over, and have been diagnosed with mucosal head and neck squamous cell carcinoma with negative surgical margins on histopathology at the Royal Darwin Hospital or the Christian Medical College, Vellore (India).
Study details:
All participants enrolled in this study will have tests carried out on tissue samples which were taken at the time of surgery, and which have already been shown to be tumour-free. These tests will assess for the presence of the two antibodies eIF4E and p53. Participants will then be followed-up for minimum of 12 months - end of study period by review of medical records, to see if any correlation exists between presence of the antibodies and cancer recurrence. It is hoped that the findings of this study may provide information on whether these antibodies may be used as a marker for prognosis in head and neck cancer patients at the time of surgery.


Trial website
Trial related presentations / publications
Joseph, S., et al. (2017). "Predictability of Recurrence using Immunohistochemistry to delineate Surgical Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study protocol for a prospective, observational and bilateral study in Australia and India." BMJ Open 7(10): e014824.
Public notes

Contacts
Principal investigator
Name 65958 0
Dr Mahiban Thomas
Address 65958 0
Department of Maxillo-facial surgery,
Royal Darwin Hospital
105 Rocklands Drive,
Tiwi
Darwin
NT 0810
Country 65958 0
Australia
Phone 65958 0
+ 61 8 8922 8888
Fax 65958 0
Email 65958 0
mahiban.thomas@nt.gov.au
Contact person for public queries
Name 65959 0
Dr Sheela Joseph
Address 65959 0
Centre for Remote Health
Corner of Simpson and Skinner street
Alice Springs
PO Box 4066
NT 0870
Country 65959 0
Australia
Phone 65959 0
+61 8 89514781
Fax 65959 0
Email 65959 0
sheela.joseph@flinders.edu.au
Contact person for scientific queries
Name 65960 0
Dr Sheela Joseph
Address 65960 0
Centre for Remote Health
Corner of Simpson and Skinner street
Alice Springs
PO Box 4066
NT 0870
Country 65960 0
Australia
Phone 65960 0
+61 8 89514781
Fax 65960 0
Email 65960 0
sheela.joseph@flinders.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary