A Randomised phase II multi-centre Trial of topical treatment in women with Vulval Intraepithelial Neoplasia

ISRCTN	ISRCTN34420460
DOI	https://doi.org/10.1186/ISRCTN34420460
Secondary identifying numbers	WCTU004; Sponsor ref: SPON CU 245

Submission date: 03/09/2007
Registration date: 25/09/2007
Last edited: 31/03/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-two-new-treatments-for-vulval-intraepithelial-neoplasia

Study website

Contact information

Prof Alison Fiander
Scientific

Department of Obstetrics and Gynaecology
Cardiff University
Heath Park
Cardiff
CF14 4XW
United Kingdom

Study information

Study design	A randomised phase II multi-centre trial.
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	A Randomised phase II multi-centre Trial of topical treatment in women with Vulval Intraepithelial Neoplasia (TR3-VIN)
Study acronym	RT3-VIN
Study hypothesis	VIN is a pre-malignant condition that predominantly affects premenopausal women. VIN has a significant invasive potential, is often highly symptomatic and difficult to manage clinically. Severe distressing symptoms of itching and pain are common and management aims to both relieve symptoms and prevent malignant progression. The precise rate of malignant progression is unknown. Surgery is often chosen as the treatment for this condition but is associated with high rates of recurrence and may be mutilating. By comparison, recent small studies of new topical treatments have shown promising results that warrant further investigation as an alternative to surgery. The purpose of this research is to determine whether there is evidence that either of the topical treatments is active, safe and feasible to use and would therefore warrant further investigation in a phase III setting.
Ethics approval(s)	To be submitted as of 03/09/2007.
Condition	Vulval Intraepithelial Neoplasia
Intervention	Topical treatment with either imiquimod or cidofovir will be applied by the patient for a maximum of 24 weeks. In both treatments the patient should use as much cream as needed to adequately cover the affected area. Patients will be reviewed every 6 weeks. At each visit the lesion will be assessed. In the absence of complete response, treatment will be continued for a maximum of 24 weeks. Arm A: Topical imiquimod will be applied three times a week. A thin layer will be spread over the area at night and the area will be washed using aqueous cream and water the following day. Patients will be advised to avoid contact with the treated area, including avoiding sexual intercourse until the area is washed the next day. Arm B: Topical cidofovir will be applied three times a week. A thin layer will be spread over the area at night and the area will be washed using aqueous cream and water the following day. Patients will be advised to avoid contact with the treated area, including avoiding sexual intercourse, until the area is washed the next day. Patients who are judged to have failed on either topical treatment will be given the opportunity to switch to the alternative trial treatment.
Intervention type	Other
Primary outcome measure	Histologically confirmed complete response by 30 weeks after start of treatment.
Secondary outcome measures	1. Symptomatic improvement, assessed at each 6-weekly visit 2. Compliance and side effects, assessed at each 6-weekly visit 3. Viral clearance, assessed 6 weeks after the participants stop treatment 4. Human PapillomaVirus (HPV) type and integration status, assessed 6 weeks after the participants stop treatment 5. Recurrence rate at two years (in 30 week complete responders). This will be assessed 6 monthly for 2 years from the end of treatment visit
Overall study start date	01/01/2008
Overall study end date	01/01/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	204 (102 in each arm)
Total final enrolment	180
Participant inclusion criteria	1. Women with biopsy proven Vulval Intraepithelial Neoplasia 3 (VIN3) (including visible peri-anal disease not extending into the anal canal) 2. At least one lesion of sufficient size to allow biopsies (greater than or equal to 1 cm2) 3. Informed consent
Participant exclusion criteria	1. Any patients with impaired renal function 2. Any patient with current anogenital carcinoma or any patient who, in the investigators opinion, is at a high risk of developing invasive disease (patients in whom invasive or microinvasive disease is suspected should have adequate biopsies to exclude this prior to entry) 3. Pregnancy, breast feeding or trying to conceive 4. Active treatment for VIN within the previous four weeks 5. Patients who are under 18 years old 6. Known allergy to either of the topical treatments 7. Unable to comply with protocol treatment 8. Prior failure of imiquimod or cidofovir following treatment 3 times a week for a minimum of 12 weeks
Recruitment start date	01/01/2008
Recruitment end date	01/01/2013

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Department of Obstetrics and Gynaecology

Cardiff
CF14 4XW
United Kingdom

Sponsor information

Cardiff University (UK)
University/education

Research and Commercial Division
7th Floor
30-36 Newport Road
Cardiff
CF24 0DE
Wales
United Kingdom

Phone	+44 (0)2920 875834
Email	DaviesKP2@cf.ac.uk
"ROR"	https://ror.org/03kk7td41

Funders

Funder type

Charity

Cancer Research UK (C10087/A7736)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2014		Yes	No
Results article	long-term follow-up results	01/08/2018	05/08/2019	Yes	No
Plain English results			31/03/2022	No	Yes

Editorial Notes

31/03/2022: Plain English results and total final enrolment added.
05/08/2019: The following changes have been made:
1. The trial acronym has been changed from "RT3 VIN" to "RT3-VIN".
2. Publication reference added.