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Trial registered on ANZCTR


Registration number
ACTRN12616000645459
Ethics application status
Approved
Date submitted
9/05/2016
Date registered
18/05/2016
Date last updated
11/04/2019
Date data sharing statement initially provided
11/04/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A prospective audit of sentinel node biopsy for vulval carcinoma in Australia and New Zealand
Scientific title
Prospective collection of clinical data following sentinel node biopsy for vulval carcinoma in Australia and New Zealand
Secondary ID [1] 289133 0
nil known
Universal Trial Number (UTN)
U1111-1182-6358
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vulval carcinoma 298634 0
Condition category
Condition code
Cancer 298700 298700 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prior to the operation and following application of emlar cream, 0.2-0.6 ml of 60-MBq technetium-99m–labeled nanocolloid (or similar) is injected by the surgeon intradermally in 4 locations around the primary tumour (0.05 ml each in each site) or clearly identifiable scar from recent excision biopsy. XRay pictures are then taken over the next 2 1/2 hours to identify the first appearing persistent focal accumulation or sentinel node. The site of the sentinel node is marked on the overlying skin.
On the day or the afternoon after the injection of the radioactive tracer, following induction of anesthesia for surgery, approximately 0.5-1.0 ml of the blue dye (eg. Patente blue-V) is injected intradermally on the same 4 locations around the primary tumor approximately 5-10 minutes prior to the surgical procedure. The surgical procedure starts with identification and removal of the sentinel nodes. During the operation a handheld gamma-ray-detection probe is used to confirm the marked area of greatest activity in the groin. A small skin incision is made at the marked spot and a sentinel node excision biopsy is performed using the handheld gamma-ray detector and by dissection of blue-stained lymph vessels. Sentinel nodes are sent to the pathologist. Subsequently resection of the vulvar lesion is performed.
Participation in this study is entirely voluntary. If women do not wish to take part in this study, they will receive one standard management of early vulval carcinoma which is wide excision or vulvectomy and removal of all groin nodes.
Intervention code [1] 294647 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298188 0
Recurrence in a groin with negative sentinel node as assessed clinically and entered on CRF
Timepoint [1] 298188 0
at the time of recurrence and/or 24 months after surgery.
Secondary outcome [1] 323441 0
Node positivity rate as assessed and entered on CRF
Timepoint [1] 323441 0
At time of sentinel node procedure and surgery
Secondary outcome [2] 323442 0
Disease recurrence at other sites as assessed clinically and entered on CRF
Timepoint [2] 323442 0
At time of recurrence and/or at 3, 12, 24, 36, 48, and 60 months after surgery
Secondary outcome [3] 323443 0
number of sentinel nodes detected using gamma-ray probe
Timepoint [3] 323443 0
at the beginning of the surgical procedure
Secondary outcome [4] 323444 0
Morbitity as assessed clinically and entered on CRF
Timepoint [4] 323444 0
At 3, 12, 24, 36, 48, and 60 months after surgery
Secondary outcome [5] 323445 0
length of Hospital stay after surgery
Timepoint [5] 323445 0
at 3 months and entered on CRF
Secondary outcome [6] 323446 0
Utility of immunohistochemistry stains entered onto CRF
Timepoint [6] 323446 0
At final data analysis

Eligibility
Key inclusion criteria
.1. Able to give informed consent.
2. Early vulval carcinoma confirmed histologically (unifocal, invasive squamous cell carcinoma less than 4cm in greatest dimension - not including insitu component)
3. Depth of invasion greater than 1mm

Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Tumour involves urethra, anus or middle 1/3 of vagina.
2. Reconstruction of the vulva using a flap has been performed with removal of the
primary lesion .
3. Clinical evidence of groin node metastasis.(palpation, imaging , FNA)
4. Prior history of SCC of the genital tract, anus, or lower body.
5. Prior groin node dissection

Study design
Purpose of the study
Treatment
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
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Statistical Considerations.
The following matters are taken into consideration.
a) Vulval carcinoma is a rare disease.
b) GROINSS study revealed a recurrence rate of 2.3% following negative sentinel nodes.
c) Expected node positivity rate between 10 and 30%
d) A groin recurrence rate of greater than 5% in women with negative sentinel nodes would be considered unacceptable.
e) Recruitment will continue until 31 August 2024. The study follow up period will continue for a minimum of 24 months (and up to 60 months) post-surgery for each woman.
Statistical review by Biostatistician Elisabeth Wells, Public Health and General Practice, University of Otago – Christchurch is reproduced below:

Sample Size for Frequency in a Population
________________________________________
Population size(for finite population correction factor or fpc)(N): 1000000
Hypothesized % frequency of outcome factor in the population (p): 3%+/-2
Confidence limits as % of 100(absolute +/- %)(d): 2%
Design effect (for cluster surveys-DEFF): 1

Sample Size(n) for Various Confidence Levels

Confidence Level(%) Sample Size
95% 280
80% 120
90% 197
97% 343
99% 483
99.9% 788
99.99% 1101

Equation
Sample size n = [DEFF*Np(1-p)]/ [(d2/Z21-a/2*(N-1)+p*(1-p)]

Results from OpenEpi, Version 2, open source calculator--SSPropor
http://www.openepi.com/SampleSize/SSPropor.htm

It would be prudent to plan the study to allow for the possibility that centres may differ somewhat, because of differences in treatment regimes or in the characteristics of patients. The statistical impact of clustering within centres is captured by the DEFF (design effect) which is the ratio of the variance of an estimate from a complex sample compared with that from a simple random sample.
DEFF = 1 + (m-1)p where m is the average cluster size (n per centre), and
p(rho) is the coefficient of intra-class correlation
Let m=13 and
p=.03 (a lowish value as patient within a centre would not be expected to be much more similar to each other than to patients at other centres)
DEFF = 1 + (13-1)*.03 = 1.36
Therefore the number required for the 95% CI to be below 5% would be 280*1.36 = 380.

Recruitment
Recruitment status
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)
NSW,QLD,TAS,WA,VIC
Recruitment hospital [1] 5728 0
Westmead Hospital - Westmead
Recruitment hospital [2] 5729 0
The Royal Women's Hospital - Parkville
Recruitment hospital [3] 5730 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 5733 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [5] 7930 0
Mater Private Hospital - South Brisbane
Recruitment hospital [6] 7931 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 15892 0
4101 - South Brisbane
Recruitment postcode(s) [2] 15893 0
2305 - New Lambton
Recruitment outside Australia
Country [1] 7850 0
New Zealand
State/province [1] 7850 0
Christchurch
Country [2] 7851 0
New Zealand
State/province [2] 7851 0
Otago
Country [3] 7852 0
New Zealand
State/province [3] 7852 0
Wellington
Country [4] 7853 0
New Zealand
State/province [4] 7853 0
Auckland

Funding & Sponsors
Funding source category [1] 293512 0
University
Name [1] 293512 0
University of Otago Christchurch
Address [1] 293512 0
Private Bag 4711
Christchurch 8140
Country [1] 293512 0
New Zealand
Funding source category [2] 293516 0
Other
Name [2] 293516 0
Robert McClelland Trust Board
Address [2] 293516 0
Estate of Robert McClelland
C/- Public Trust Charitable Services, Private Bag 17906, Greenlane, Auckland. 1546
Country [2] 293516 0
New Zealand
Funding source category [3] 293517 0
Charities/Societies/Foundations
Name [3] 293517 0
GRACI Foundation (The Gynaecological Cancer Research Trust)
Address [3] 293517 0
PO Box 36665, Merivale, Christchurch. 8146
Country [3] 293517 0
New Zealand
Funding source category [4] 302476 0
Charities/Societies/Foundations
Name [4] 302476 0
Australian Society of Gynaecologic Oncologists (ASGO)
Address [4] 302476 0
ASGO Secretariat
c/o YRD Event Management
PO Box 717, Indooroopilly, QLD 4068, AUSTRALIA
Country [4] 302476 0
Australia
Primary sponsor type
University
Name
University Of Otago Christchurch
Address
Private Bag 4711
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 292340 0
None
Name [1] 292340 0
Address [1] 292340 0
Country [1] 292340 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294958 0
HDEC Multi-region ethics Committee
Ethics committee address [1] 294958 0
PO Box 5013
Wellington 6145
Ethics committee country [1] 294958 0
New Zealand
Date submitted for ethics approval [1] 294958 0
01/06/2010
Approval date [1] 294958 0
31/08/2010
Ethics approval number [1] 294958 0
MEC/10/07/063

Summary
Brief summary
This study aims to prospectively collect clinical data following sentinel node biopsy for vulval carcinoma in Australia and New Zealand. You may be eligible to join this study if you are a female aged 18 years or above with histologically confirmed, unifocal invasive squamous cell carcinoma of vulva less than 4cm in greatest dimension.
Women in Australia and New Zealand women with early vulval cancer will be offered sentinel node procedures in place of groin node dissection.
On the day before or the morning of your operation, you will have a small injection of a radioactive marker into the skin next to the cancer. A local anaesthetic cream will be used to reduce any discomfort from this injection. Pictures will then be taken over the next 2 1/2 hours to see which glands the marker has spread to. The marker will also help us find the ‘sentinel nodes’ during your operation.
Either on the afternoon after the injection or the next day you will have your operation as planned by your doctor. Whilst you are asleep we will inject some blue dye around the cancer which will also help us to identify the sentinel glands. During the 60 minute operation we will remove the cancer. We will identify and remove the sentinel lymph gland(s) from one or both groins. When sentinel nodes in one or two groins can not be identified a full removal of the groin nodes (lymphadenectomy) on either one or both sides will be performed. The gland(s) will be sent to the laboratory for detailed assessment by the pathologist.
Follow up clinical data will be collected from your clinical records at 3, 12, and 24 months after surgery (and at, 36, 48, and 60 months where possible), from information obtained when you attend outpatients clinic.
The majority of women with early vulval carcinoma do not have groin node metastasis and these women are unlikely to benefit from groin node dissection. The use of sentinel node dissection is safe and should be part of the standard treatment for women with early stage vulvar cancer.
Trial website
Trial related presentations / publications
Sykes PH. et al. (2015) Abstract presentation at ANZGOG Annual Scientific Meeting. Groin Recurrence Following Negative Sentinel Node Biopsy. A report from the “Prospective Audit of Sentinel Node Biopsy for Vulval Cancer in Australia and New Zealand” Sykes PH et al. (2016) Abstract presentation at ASGO Annual Scientific Meeting. The crucial nature of pathology in sentinel node biopsy procedures for vulvar cancer.
Public notes

Contacts
Principal investigator
Name 65598 0
A/Prof Peter Hugh Sykes
Address 65598 0
Department of O & G
University of Otago - Christchurch
2 Riccarton Avenue
Private Bag 4711
Christchurch 8140
Country 65598 0
New Zealand
Phone 65598 0
+64 3 364 4630
Fax 65598 0
+64 3 364 4634
Email 65598 0
peter.sykes@otago.ac.nz
Contact person for public queries
Name 65599 0
Ms Dianne Harker
Address 65599 0
Dept O & G
University of Otago - Christchurch
Christchurch Women's Hospital
2 Riccarton Avenue
Private Bag 4711
Christchurch 8140
Country 65599 0
New Zealand
Phone 65599 0
+64 3 364 4624
Fax 65599 0
+64 3 364 4634
Email 65599 0
dianne.harker@otago.ac.nz
Contact person for scientific queries
Name 65600 0
A/Prof Peter Sykes
Address 65600 0
Dept O & G
University of Otago - Christchurch
Christchurch Women's Hospital
2 Riccarton Avenue
Private Bag 4711
Christchurch 8140
Country 65600 0
New Zealand
Phone 65600 0
+64 3 364 4630
Fax 65600 0
+64 3 364 4634
Email 65600 0
peter.sykes@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We did not indicate that we would be sharing IPD when we applied for ethical approval for our study. There are no plans for IPD sharing.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
No Results