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Trial registered on ANZCTR


Trial ID
ACTRN12613001207707
Ethics application status
Approved
Date submitted
28/10/2013
Date registered
4/11/2013
Date last updated
16/06/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Compass Trial: A Randomised Controlled Trial of Primary Human Papillomavirus (HPV) Testing for Cervical Cancer Screening in Australia: Pilot Study
Scientific title
Pilot Study for a trial in Human Papillomavirus (HPV) vaccinated and unvaccinated women presenting for cervical screening of 6 yearly HPV screening versus 3-yearly cytology screening to assess the feasibility via recruitment rates, cross sectional positivity rate and laboratory implementation.
Secondary ID [1] 282515 0
Nil
Universal Trial Number (UTN)
Trial acronym
Compass
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical cancer 289178 0
Human Papillomavirus (HPV) 290408 0
Condition category
Condition code
Cancer 289499 289499 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention Arm 2: Five -yearly HPV screening with types 16/18 (+/-45 in pilot study) genotyping and cytology triage of intermediate risk women with other oncogenic HPV infection; The sample collected from participants in intervention arm 2 will be a Liquid Based Cytology (LBC) Pap test and collection should take 15 minutes and

Intervention Arm 3: Five -yearly HPV screening with types 16/18 (+/-45 in pilot study) genotyping and dual-stained (DS) cytology (with p16/Ki67) triage of intermediate risk women with other oncogenic HPV infection. The sample collected from participants in intervention arm 3 will be a Liquid Based Cytology (LBC) Pap test and collection should take 15 minutes
Intervention code [1] 287175 0
Early detection / Screening
Comparator / control treatment
Arm 1: Two and a half -yearly image read cytology screening with reflex HPV triage testing for low grade (p/d LSIL) smears. The sample collected from participants in Arm 1 will be a Liquid Based Cytology (LBC) Pap test and collection should take 15 minutes
Control group
Active

Outcomes
Primary outcome [1] 290545 0
1). To assess participant acceptance of the randomisation process and use of longer routine screening intervals, via recruitment rate.
Timepoint [1] 290545 0
3, 6, 12 months
Primary outcome [2] 290793 0
2). To confirm the operational feasibility of laboratory processing procedures for each of the two HPV test platforms.
Timepoint [2] 290793 0
12 months

Total laboratory processing start time will be defined as time and date a sample is received and logged at specimen reception to the time when the final report is entered into the laboratory electronic database. Total sample processing time (TPT) will be defined as the time from specimen load to HPV result being available on the manufacturer’s output. For hands-on time (HOT), an RA will observe and record the start and stop of the hands-on processing times. A minimum of three sample runs/batches per test (up to ~90 test samples per run) will be conducted. The average results across the three runs will be taken to derive averages of the three key measures for each technology.

The time and motion study will be conducted after suitable run in and lab verification has been performed for each technology. In the pilot study it is unlikely that the full batch capacity will be utilised, due to the need to report in a timely fashion. Therefore adjustments will be made to allow for components of the processing time that are dependent on the number of individual samples versus automated components of the processing time that are independent of the number of samples being processed.

For DS, HOT for preparation of the stain using an immunostainer will be quantified. Reading/scanning with microscopy time will also be quantified.

Similar processes will be followed for quantifying HOT and TOT in the cytology arm.
Primary outcome [3] 290794 0
3). To assess positivity rates for the primary screening test in each arm, and estimate the cross sectional sensitivity and specificity of each screening approach for the detection of CIN 2+ and CIN 3+.
Timepoint [3] 290794 0
Baseline

Using participant’s Round One screening test results, obtained from VCS Pathology, we will estimate the test positivity rates by age (overall, <30 and 30+) for the primary screening test in each arm (Cytology: HPV: HPV).

Using test result data from screen negative women that were referred for colposcopy as part of the verification colposcopy arm we will estimate the cross-sectional sensitivity and specificity of each primary screening test (Cytology: HPV: HPV). These data will be collected at the time of colposcopy, by attending specialists, and recorded by the VCCR.
Secondary outcome [1] 305299 0
4). To estimate the sensitivity and specificity of DS testing, in women positive for HPV
Timepoint [1] 305299 0
Baseline

Eligibility
Key inclusion criteria
Australian female resident of Victoria
Aged 25-64
Attending for routine cervical screening at a participating health care practice
Minimum age
25 Years
Maximum age
64 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Total hysterectomy (uterus and cervix)
Presence of symptoms for which cervical cancer must be excluded
Currently undergoing treatment for cervical pre-cancer, or cancer
Attending for follow-up of a prior cervical abnormality, including repeated "test of cure" procedures in which the woman has not yet been discharged back to routine screening
Known pregnancy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Practitioners will approach patients during regular cervical screening visits.

Prior to performing the cervical screening examination, the practitioner will assess patient eligibility and where appropriate, seek consent for participation in the study. The Practitioner will provide participants with an information sheet to read and ask questions.

Women who provide consent will have a cervical smear collected using a Liquid Based Cytology ThinPrep PreservCyt vial. The LBC sample will be labelled with the woman's name and date of birth, placed in a sample bag, along with the consent form, and returned to a centralised processing laboratory at VCS Pathology.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Upon receipt and logging of the sample at VCS pathology, individual subject allocation to one of three study arms will be performed. Randomisation will be performed using a computer-generated randomisation sequence which will be overseen by the NHMRC Clinical Trials Centre. Randomisation will be at 1:2:2 ratio (cytology:HPV:HPV)

Randomisation will only be performed once subject eligibility has been confirmed. Automatic checks will also be made against the laboratory database that the woman has not previously been enrolled in the trial.

Neither the participant nor practitioner will be aware of subject allocation at the time of recruitment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety
Statistical methods / analysis
The pilot study will involve recruiting 5,000 women aged 25-64 years. In early 2012, the Victorian Cytology Service (VCS) Pathology Liaison Physicians provided a comprehensive list of all general practices with close links to VCS. Pathology. From the list, 6 eligible practices were identified and have agreed to participate in the trial. These clinics report approximately 6,300 Pap tests from age eligible women per year. We will be actively recruiting new clinics over the duration of the pilot.

Using data on the number of cervical screening samples sent to VCS Pathology in 2012 by each participating clinic, we estimated the expected number of women aged 25 – 29 and 30 – 64 years that would be enrolled in the pilot study if the recruitment rates were 65% and 50% overall, and if these recruitment rates were also sustained by each individual clinic.

The target recruitment rate for participating individual practitioners will be 50% or greater, and if overall recruitment in the pilot is less than 50%, study materials will be reviewed and additional focus groups may be held with practitioners and patients during the course of the pilot

Recruitment
Recruitment status
Active, not 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)
VIC
Recruitment postcode(s) [1] 7487 0
3068 - Clifton Hill
Recruitment postcode(s) [2] 7488 0
3442 - Woodend
Recruitment postcode(s) [3] 7489 0
3000 - Melbourne
Recruitment postcode(s) [4] 7491 0
3107 - Templestowe Lower
Recruitment postcode(s) [5] 7492 0
3437 - Gisborne
Recruitment postcode(s) [6] 7493 0
3146 - Glen Iris
Recruitment postcode(s) [7] 7494 0
3053 - Carlton

Funding & Sponsors
Funding source category [1] 288007 0
Charities/Societies/Foundations
Name [1] 288007 0
The Cancer Research Division- Cancer Council New South Wales
Address [1] 288007 0
Cancer Council New South Wales, 153 Dowling Street, Woolloomooloo, NSW 2011
Country [1] 288007 0
Australia
Funding source category [2] 288008 0
Other
Name [2] 288008 0
Victorian Cytology Service
Address [2] 288008 0
265 Faraday Street Carlton, VIC 3053
Country [2] 288008 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Roche Molecular Systems Inc. and
Address
4300 Hacienda Drive, Pleasanton, California 94588, USA
Country
United States of America
Secondary sponsor category [1] 286729 0
Commercial sector/Industry
Name [1] 286729 0
Ventana Medical Systems
Address [1] 286729 0
1910 E.Innovation Park Drive, Tuscon, Arizona, 85755, USA
Country [1] 286729 0
United States of America
Other collaborator category [1] 277679 0
Individual
Name [1] 277679 0
Prof Karen Canfell (co-PI)
Address [1] 277679 0
Cancer Council New South Wales, 153 Dowling Street, Woolloomooloo, NSW 2011
Country [1] 277679 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289931 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 289931 0
Alfred Health, 55 Commercial Road, Melbourne, VIC, 3004
Ethics committee country [1] 289931 0
Australia
Date submitted for ethics approval [1] 289931 0
26/03/2013
Approval date [1] 289931 0
30/08/2013
Ethics approval number [1] 289931 0
HREC/13/Alfred/1 Local Project 111/13
Ethics committee name [2] 289932 0
Royal Australian College of General Practitioners, National Research and Evaluation Ethics Committee
Ethics committee address [2] 289932 0
100 Wellington Parade, East Melbourne, Victoria 3002
Ethics committee country [2] 289932 0
Australia
Date submitted for ethics approval [2] 289932 0
13/05/2013
Approval date [2] 289932 0
04/09/2013
Ethics approval number [2] 289932 0
NREEC 13-005
Ethics committee name [3] 295396 0
Bellberry Limited
Ethics committee address [3] 295396 0
129 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [3] 295396 0
Australia
Date submitted for ethics approval [3] 295396 0
02/09/2015
Approval date [3] 295396 0
14/10/2015
Ethics approval number [3] 295396 0
2015-08-579

Summary
Brief summary
The study is evaluating whether testing for certain types of Human Papillomavirus (HPV) is a more effective cervical cancer screening test than the Pap Smear test.
Who is it for?
You may be eligible to join this study if you are female, aged between 25 years and 64 years, an Australian resident in Victoria, and attends routine cervical screenings at one of the study’s participating health care practice.
Trial details
Participants in this study will be randomly (by chance) divided into one of three groups. Participants in one group will undergo three-yearly image read cytology screening with reflex HPV triage testing for low grade Possible/Definite Low-Grade Squamous Intraepithelial Lesion (p/d LSIL) smears. Participants in the second group will undergo six-yearly HPV screening with types 16/18 (+/- 45 in pilot study) genotyping and cytology triage of intermediate risk women with other oncogenic HPV infection. Participants in the third group will undergo a six-yearly HPV screening with types 16/18 (+/- 45 in pilot study) genotyping and dual-stained (DS) cytology (with p16/Ki67) triage of intermediate risk women with other oncogenic HPV infection.

Trial website
www.compasstrial.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40034 0
A/Prof Marion Saville (co-Principal Investigator)
Address 40034 0
Marion Saville
Victorian Cytology Service
265 Faraday Street, Carlton, VIC, 3053
Country 40034 0
Australia
Phone 40034 0
+61 3 9250 0322
Fax 40034 0
Email 40034 0
msaville@vcs.org.au
Contact person for public queries
Name 40035 0
Miss Jessica Darlington-Brown
Address 40035 0
Cancer Council New South Wales, 153 Dowling Street, Woolloomooloo, New South Wales, 2011
Country 40035 0
Australia
Phone 40035 0
+61 2 9334 1419
Fax 40035 0
Email 40035 0
Jessica.DB@nswcc.org.au
Contact person for scientific queries
Name 40036 0
Prof Karen Canfell
Address 40036 0
Cancer Council New South Wales, 153 Dowling Street, Woolloomooloo, New South Wales, 2011
Country 40036 0
Australia
Phone 40036 0
+61 2 9334 1726
Fax 40036 0
Email 40036 0
karen.canfell@nswcc.org.au