Plain English Summary
WCTU004; Sponsor ref: SPON CU 245
A Randomised phase II multi-centre Trial of topical treatment in women with Vulval Intraepithelial Neoplasia (TR3-VIN)
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.
To be submitted as of 03/09/2007.
A randomised phase II multi-centre trial.
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Vulval Intraepithelial Neoplasia
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.
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.
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.
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 trial start date
Overall trial end date
Reason abandoned (if study stopped)
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
Target number of participants
204 (102 in each arm)
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
Recruitment end date
Countries of recruitment
Trial participating centre
Department of Obstetrics and Gynaecology
Cardiff University (UK)
Research and Commercial Division
30-36 Newport Road
+44 (0)2920 875834
Cancer Research UK (C10087/A7736)
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Tristram A, Hurt CN, Madden T, Powell N, Man S, Hibbitts S, Dutton P, Jones S, Nordin AJ, Naik R, Fiander A, Griffiths G, Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT(3)VIN): a multicentre, open-label, randomised, phase 2 trial., Lancet Oncol., 2014, doi: 10.1016/S1470-2045(14)70456-5.