ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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

ACTRN12617000930381

Ethics application status

Approved

Date submitted

1/06/2017

Date registered

27/06/2017

Date last updated

28/10/2019

Date data sharing statement initially provided

23/07/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Observational management of young women under the age of 25 with cervical intraepithelial neoplasia (CIN3)

Scientific title

A prospective multicentre trial of observational management of CIN3 in women under the age of 25: safety and rate of spontaneous regression

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1197-2845

Trial acronym

CIN3MA

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cervical Intraepithelial Neoplasia (CIN) 3

Condition category

Condition code

Cancer

Cervical (cervix)

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Observational management of Cervical Intraepthelial Neoplasia (CIN) grade 3 in women aged under 25 years for 12 months i.e., 6-monthly colposcopy examination with a directed cervical biopsy (histology), and cervical smear (cytology) undertaken by a trained colposcopist at a hospital-based colposcopy clinic for a total of 1 year (or until the woman turns 25 years old, whichever is sooner).

Attention will be paid to ensure the whole transformation zone and lesion are seen and that there is no colposcopic evidence of glandular or invasive disease. If a lesion persists, representative biopsies must be taken, two if possible and one from each quadrant in larger lesions. If the colposcopy is normal, we encourage the taking of a biopsy from the transformation zone in the previously affected area.

Treatment is indicated if the patient becomes symptomatic, there is colposcopic or cytological suspicion of invasive or glandular disease, the colposcopy is unsatisfactory and abnormal cytology persists, the histology is reported as invasive or glandular disease, the patient requests treatment, turns 25 years old without demonstrating persistent regression, or is unable to attend further follow up and the lesion persists. If treatment is performed a trial Completion Form is filled in and the patient subsequently managed as per normal practice.

If CIN2 or 3 persists, or cytology is reported as ASCH or HSIL, colposcopy should be repeated at 6 monthly intervals for 1 year. If CIN2 or 3, or ASCH or HSIL cytology persists, at this point, the patient should be treated. At this point, a trial Completion form is filled in.

Regression is:
- normal colposcopy, normal/low grade cytology, no biopsy taken OR
- normal colposcopy, normal/low grade cytology, normal/low grade histology OR
- low grade colposcopy, normal/low grade cytology, normal/low grade histology OR
- CIN 2 colposcopy but normal/low grade cytology, normal/low grade histology

Regression is not confirmed:
- CIN 3 colposcopy but normal/low grade cytology, normal/low grade histology
- if a lesion is present and a biopsy not taken
- if cytology is ASCH or worse or
- a smear is not taken or unsatisfactory

If regression is documented women must have a follow-up at 6 months with;
- a repeat colposcopy and smear and
- a biopsy if a lesion is present

If following the repeat colposcopy, criteria for regression is again met, the lesion has demonstrated persistent regression.

Following persistent regression and after discussion between the colposcopist and the woman, the patient may be discharged from the colposcopy clinic. If this is the case, a trial Completion Form is filled and follow-up is then as per National Cervical Screening Programme (NCSP) guidelines following high grade abnormality with a smear in 6 months (by primary smear taker). If the woman is not discharged from colposcopy clinic, a repeat colposcopy occurs at 6-12 months. Management should be based on the NCSP guidelines.

If regression is demonstrated at the 12 month follow up for the first time, the colposcopist will discuss either immediate treatment or follow up at 6 months. However at this point, a trial Completion form will be filled in, and the patient subsequent management should be based on the results of this colposcopy and the NCSP guidelines.

If following apparent regression, at the next follow up CIN2 or worse is seen or cytology is reported as ASCH or worse, 6 monthly follow up must continue unless the woman elects to be treated or continues on the trial protocol.

Intervention code [1]

Treatment: Other

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Proportion of participants whose lesions regress to CIN1 or less.

Regression is defined as return to normal/low grade cytology and histology, and persistent regression is defined as regression on two or more successive 6 monthly visits.

Timepoint [1]

Every 6 months for 12 months

Primary outcome [2]

Proportion of participants who progress to microinvasive or invasive cancer.

Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system. Microinvasive cancer (also known as Stage 1A) is a lesion in which neoplastic cells invade the stroma, in one or more sites, with a maximum depth of 5.0 mm below the base of the epithelium and maximum width of 7.0 mm, without lymphatic or blood vessel involvement. The depth of invasion should be measured from the base of the epithelium, either surface or glandular, from which it originates. Microinvasive cancer (stage IA) can be further subdivided into stages 1A1 and 1A2. Stage 1A1 encompasses stromal invasion <3.0 mm in depth and <7.0 mm in width, while stage 1A2 encompasses stromal invasion >3.0–5.0 mm in depth and <7.0 mm in width.

Invasive cancer (>Stage 1A) is a lesion in which neoplastic cells invade the stroma with a depth greater than 5.0 mm.

Timepoint [2]

Every 6 months for 12 months

Primary outcome [3]

Proportion of participants who require treatment (by review of medical records)

Timepoint [3]

Every 6 months for 12 months

Secondary outcome [1]

Proportion of participants who are lost to follow up (greater than 9 months)

Timepoint [1]

Every 6 months for 12 months

Secondary outcome [2]

Proportion of eligible women <25 years with CIN3 included in the trial (and reasons for exclusion) - this is a composite outcome

Timepoint [2]

At the end of the recruitment period

Eligibility

Key inclusion criteria

- Age under 25 at date of initial biopsy.
- Attending colposcopy clinic as a result of an abnormal smear but without a history of prior high grade abnormality.
- Biopsy proven CIN3 (or CIN2/3).
- Entire lesion accessible to colposcopy.
- Participants in trial agree to six monthly colposcopy and cervical smear and biopsy for a total of two years.
- Cytology and pathology reviewed and CIN3 confirmed at a multidisciplinary meeting and no other clinical factor was identified that would exclude them from the trial.
- Signed informed consent

Minimum age

15 Years

Maximum age

24 Years

Sex

Females

Can healthy volunteers participate?

Key exclusion criteria

- High grade cytological or histological abnormality prior to this referral.
- Unsatisfactory colposcopy.
- Large complex colposcopic abnormality where adequate histological sampling difficult.
- Cytology suspicious of invasion or glandular abnormality.
- Patients unwilling or unable to attend follow up.
- Patients whose cytology and histology have not been reviewed at MDM.
- Clinical suspicion of invasion or AIS.
- Any glandular histological or cytological abnormality.
- Concern on behalf of treating doctor that patient is unlikely to attend follow up.
- Immunosuppression.
- Pregnancy
- Post-coital bleeding or any other irregular vaginal bleeding not attributable to oral contraceptive related break through bleeding

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

Statistical methods / analysis

The pilot study objective is to provide clinically relevant information on the safety and practicality of observational management of CIN3 from a prospective 2-centre trial.
The primary aims of the pilot study are to document over 12 months, for a cohort of n=50 women under the age of 25 with a diagnosis of CIN3;
- Safety of delayed identification and treatment of CIN3 in young women,
- Recruitment rate, and
- Spontaneous rate of regression.
Data analysis will be completed centrally once all patients have completed 12 months follow up.
Primary outcome measures will be primarily descriptive and will include proportion of participants:
- whose lesions regress to CIN1 or less at both follow up visits (i.e., at 6 months and 12 months) – persistent regression.
- whose lesions regress to CIN1 or less at 12 months – single regression.
- whose lesions remain high grade at 12 months (i.e., CIN2 or CIN3).
- who progress to microinvasive or invasive cancer.
- who require treatment (and reason for treatment).
- who are lost to follow up (greater than 9 months).

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Lack of funding/staff/facilities
Participant recruitment difficulties
Safety concerns

Date of first participant enrolment

Anticipated

3/09/2018

Actual

18/10/2018

Date of last participant enrolment

Anticipated

31/12/2019

Actual

27/06/2019

Date of last data collection

Anticipated

27/06/2020

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Waikato, Canterbury

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Otago - Christchurch

Address [1]

Private Bag 4711
Christchurch 8140

Country [1]

New Zealand

Funding source category [2]

Hospital

Name [2]

Canterbury District Health Board

Address [2]

Private Bag 4710
Christchurch 8140

Country [2]

New Zealand

Funding source category [3]

Government body

Name [3]

Lottery Health Research

Address [3]

Department of Internal Affairs
45 Pipitea Street
Wellington 6011
PO Box 805
Wellington 6140

Country [3]

New Zealand

Primary sponsor type

University

Name

University of Otago, Christchurch

Address

Private Bag 4711
Christchurch 8140

Country

New Zealand

Secondary sponsor category [1]

Hospital

Name [1]

Canterbury District Health Board

Address [1]

Private Bag 4710
Christchurch 8140

Country [1]

New Zealand

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health and Disability Ethics Committee

Ethics committee address [1]

Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6140

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

13/04/2018

Approval date [1]

05/07/2018

Ethics approval number [1]

16/STH/201/AM03

Summary

Brief summary

In 2018, the NZ cervical screening age will increase from 20 to 25 years. This will lead to a delay in the diagnosis and treatment of high grade cervical abnormalities in young women of up to 5 years. Cervical cancer is rare in young women and cervical screening in women aged 20-24 has been shown to have little to no impact on rates of invasive cervical cancer up to age 30. Despite this, currently, ~1100 NZ women aged 20-24 years are diagnosed with high grade cervical cell abnormalities (CIN2 and 3) each year. Usually these women are treated and we have a poor understanding of the impact of deferred diagnosis on these lesions. However, there is growing evidence that a high proportion of CIN2 lesions naturally resolve in young women. In contrast, data regarding CIN3 regression rates are lacking and the impact of delayed CIN3 diagnosis and treatment in young women is poorly understood. 
The primary aims of the pilot study are to document over 12 months, for a cohort of n=50 women under the age of 25 with a diagnosis of CIN3; safety of delayed identification and treatment of CIN3 in young women, recruitment rate, and to give an indication of CIN3 regression rates. Women <25 years with biopsy-diagnosed CIN3 (including CIN2/3) will be identified in large colposcopy centres in NZ and invited to participate. Pathology and cytology specimens will be reviewed at a multidisciplinary meeting. Provided they meet eligibility criteria, consenting women will undergo observational management (i.e., repeat colposcopy, cytology, and cervical biopsy performed every 6 months for up to 12 months). Treatment is indicated if the patient becomes symptomatic, there is suspicion of invasive or glandular disease, the patient requests treatment, the patient completes 12 months follow-up or at their first follow-up after their 25th birthday (whichever is sooner) without demonstrating persistent regression. Regression is defined as two consecutive colposcopy follow-ups showing CIN1 or less. The trial will be terminated prematurely if; invasive carcinoma of the cervix (>1a) is diagnosed in any study participant; or microinvasive squamous carcinomas are diagnosed >2% of study participants.  Primary outcome measures: Proportion of participants 1) whose lesions regress to CIN1 or less, 2) who progress to invasion, 3) who require treatment, and 4) who are lost to follow up.  We hypothesise that CIN3 observational management can be safely performed for women aged less than 25 years and that within this hypothesis, we estimate that no women will develop >1a carcinoma, <5% of participants will be lost to follow up and the recruitment rate will be at least 40% of eligible participants.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Peter Sykes

Address

Department of Obstetrics & Gynaecology
University of Otago, Christchurch
Christchurch Women's Hospital
Private Bag 4711
Christchurch 8140

Country

New Zealand

Phone

+64 3 364 4647

Fax

peter.sykes@otago.ac.nz

Contact person for public queries

Name

Peter Sykes

Address

University of Otago, Christchurch
Christchurch Women's Hospital
Private Bag 4711
Christchurch 8140

Country

New Zealand

Phone

+64 3 364 4647

Fax

peter.sykes@otago.ac.nz

Contact person for scientific queries

Name

Peter Sykes

Address

University of Otago, Christchurch
Christchurch Women's Hospital
Private Bag 4711
Christchurch 8140

Country

New Zealand

Phone

+64 3 364 4647

Fax

peter.sykes@otago.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

IPD not planned

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
3214	Informed consent form			carrie.innes@otago.ac.nz
3215	Study protocol			carrie.innes@otago.ac.nz

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically