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Compass - Randomised Controlled Trial of Primary HPV Testing for Cervical Screening in Australia (Compass)

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02328872
Recruitment Status : Active, not recruiting
First Posted : December 31, 2014
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
Cancer Council New South Wales
Information provided by (Responsible Party):
Marion Saville, VCS Foundation

Brief Summary:
Compass is a randomised controlled trial of primary HPV testing for cervical cancer screening in Australia. A pilot study involving 5,000 women was carried out in 2013-2014. The trial will involve recruiting 76,300 women from primary health clinics. Women aged 25-69, attending for cervical screening or for routine follow-up will be invited to participate in the 2-arm trial. A liquid-based cytology (LBC) sample will be taken from consenting women and sent to VCS Pathology. Women will be randomised in a 1:2 parallel group allocation to LBC and HPV arms using randomisation with the minimisation procedure, with stratification by birth cohort according to whether offered HPV vaccination in Australia's national publicly-funded HPV vaccination program (date of birth >=July 1st 1980 and <1st July 1980). In the LBC (active control) arm, women will undergo 2.5 yearly image read cytology screening with reflex HPV triage testing for low grade cytology. In the HPV (intervention) arm women will undergo 5 yearly HPV screening with partial genotyping enabling separate identification of HPV16 and HPV18 and referral of this group for diagnostic evaluation, and secondary randomisation of "intermediate risk" women testing positive for oncogenic HPV (but not HPV 16 or 18) to either image read LBC screening or dual-stained (DS) cytology testing with p16/Ki67. The laboratory reports issued to practitioners will specify the recommended management for women, according to study arm and test results.Participating women will be flagged and clinical outcomes will be tracked via the Compass Register. Data linkage between the Compass Register and HPV vaccination records held on the Australian Immunisation Register will be performed in order to integrate vaccination and screening histories for trial participants. Participants will be actively followed for an anticipated 5 years from the time of recruitment and the primary outcome is based on the total cumulative detection of CIN3+ after exit testing at 5 years.

Condition or disease Intervention/treatment Phase
Cancer of the Cervix Cervical Intraepithelial Neoplasia Device: Molecular testing for HPV Device: Liquid Based Cytology Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Compass - Randomized Controlled Trial of 5-yearly Cervical Screening With Primary HPV Testing Versus Cervical Screening With 2.5-yearly Liquid Based Cytology Testing, in HPV-Unvaccinated and HPV-Vaccinated Women in Australia
Study Start Date : January 2015
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention (HPV Arm)
Molecular testing for HPV with partial genotyping for types 16/18, with referral of the HPV16/18-positive group for diagnostic evaluation, and secondary randomisation of women testing positive for other oncogenic HPV infection (not 16/18), to either image-read cytology screening or dual-stained (DS) cytology testing with p16/Ki67 - the "HPV arm". Screening performed 5 yearly.
Device: Molecular testing for HPV
Molecular testing for HPV with a test allowing partial genotyping for separate identification of types 16/18 from cervical samples. The technology used in this trial will be approved by the Therapeutic Goods Administration (TGA) Australia. It will identify the major HPV oncogenic genotypes in a pool and separately identify HPV 16 and 18. It will also satisfy performance criteria for relative sensitivity and specificity compared to Hybrid Capture 2 (HC2 ) as articulated by Meijer et al, 2009, Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older.

Active Comparator: Control (LBC Arm)
Image-read liquid based cytology (LBC) screening with reflex HPV triage testing for low grade smears, the "LBC arm." Screening performed 2.5 yearly.
Device: Liquid Based Cytology
The liquid based cytology (LBC) used in this trial will be will be approved by the Therapeutic Goods Administration (TGA) Australia for LBC and appropriately validated and (TGA approved) to perform human papillomavirus testing from a cytology sample.




Primary Outcome Measures :
  1. Cumulative CIN3+ (Cervical Intraepithelial Neoplasia Grade 3 or invasive cervical cancer) (ITT) [ Time Frame: Expected 5 year follow-up ]
    The primary outcome will be cumulative CIN3+ at 5 years following a 5 year HPV exit testing round in both arms, in women randomised to the HPV arm vs. women randomised to the LBC arm, adjusted for censoring after CIN2+ treatment. For the primary outcome, intention to treat analysis will be performed with closed loop testing for non-inferiority and superiority if non-inferiority is declared. Assuming a total average CIN3+ rate in the LBC arm (across unvaccinated and vaccinated women) of 0.94%, and an absolute non-inferiority margin of 0.22%, the trial will have 78% power with 97.5% confidence to detect non-inferiority for the HPV arm, allowing for a 15% non-compliance rate.


Secondary Outcome Measures :
  1. Cumulative CIN3+ in baseline screen-negative women (ITT) [ Time Frame: Expected 5 year follow-up ]
    Cumulative CIN3+ in women presenting for routine screening randomised to the HPV arm who were HPV-negative at baseline, vs. CIN3+ in those randomised to the LBC arm and who were LBC-negative at baseline, adjusted for censoring after CIN2+ treatment and stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980). Intention to treat analysis will be performed with closed loop testing for non-inferiority and superiority if non-inferiority is declared.

  2. Cumulative CIN3+ in baseline screen-negative women (per protocol) [ Time Frame: Expected 5 year follow-up ]
    Cumulative CIN3+ in women presenting for routine screening randomised to the HPV arm who were HPV-negative at baseline, vs. CIN3+ in those randomised to the LBC arm and who were LBC-negative at baseline and at 2.5 years, adjusted for censoring after CIN2+ treatment and stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980). Per-protocol analysis will be performed in women screened and followed up within a defined tolerance period according to protocol recommendations.

  3. Cumulative CIN2+ in baseline screen-negative women (ITT) [ Time Frame: Expected 5 year follow-up ]
    Cumulative CIN2+ in women randomised to the HPV arm who were HPV-negative at baseline, vs. CIN2+ in women who were randomised to the LBC arm and were LBC-negative at baseline, adjusted for censoring after CIN2+ treatment and stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980).

  4. Baseline CIN2+ and CIN3+ [ Time Frame: Following recruitment ]
    Cross-sectional outcomes for CIN 2+ and CIN3+ detection in each arm, stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980).

  5. CIN2+ in women randomised to HPV testing at baseline with other oncogenic HPV [ Time Frame: Expected 12-24 month follow-up ]
    CIN2+ in women randomised to HPV testing at baseline who have other HPV (not 16/18), stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980).

  6. CIN2+ and CIN3+ in women who have an abnormal test result at baseline [ Time Frame: Expected 5 year follow-up ]
    CIN2+ and CIN3+ in women who have an abnormal test result at baseline, adjusted for censoring after CIN2+ treatment and stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980).

  7. CIN2+ and CIN3+ in women who were in follow-management for a previous abnormality at baseline [ Time Frame: Expected 5 year follow-up ]
    CIN2+ and CIN3+ in women who were in follow-management for a previous abnormality at baseline, adjusted for censoring after CIN2+ treatment and stratified by recruitment group (date of birth >=July 1st 1980 and <1st July 1980).



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Ages Eligible for Study:   25 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Australian female residents aged 25-69 years who are attending for routine cervical screening. (Note: since April 2016 recruitment has been confined to the younger strata, i.e. women age-eligible for HPV vaccination aged at least 25 and born on or after 1st July 1980, as the recruitment target of the older cohort was met).
  • Participants may have been previously enrolled in the Compass Pilot but must have been discharged to routine screening. Women may also be in follow-up management for a previous abnormality or unsatisfactory cytology.

Exclusion Criteria:

  • Previous total hysterectomy (uterus and cervix).
  • The presence of symptoms or signs for which cervical cancer must be excluded.
  • Currently undergoing treatment for cervical cancer.
  • Currently enrolled in the Compass Pilot Study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02328872


Locations
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Australia, Victoria
VCS Foundation
Carlton, Victoria, Australia, 3053
Sponsors and Collaborators
VCS Foundation
Cancer Council New South Wales
Investigators
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Principal Investigator: Karen Canfell, BE, D.Phil. Cancer Council New South Wales
Principal Investigator: Marion Saville, M.B., Ch.B VCS Foundation
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Marion Saville, Associate Professor, VCS Foundation
ClinicalTrials.gov Identifier: NCT02328872    
Other Study ID Numbers: Exec-PP-12
First Posted: December 31, 2014    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020
Keywords provided by Marion Saville, VCS Foundation:
screening
cervical screening
Human Papillomavirus (HPV)
cancer prevention
Additional relevant MeSH terms:
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Cervical Intraepithelial Neoplasia
Uterine Cervical Neoplasms
Neoplasms
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases