Primary treatment with imiquimod versus surgery for vulvar intraepithelial neoplasias

Title: Primary Imiquimod Treatment versus Surgery for Vulvar Intraepithelial Neoplasia Study design: Prospective randomized controlled multicenter trial; patient oriented non-profit clinical study Aim: to evaluate the efficacy, defined as complete clinical response 6 months after treatment start, of Imiquimod compared to the standard treatment (surgery) for VIN Trial Cites: Multi-Centre, AGO-Austria Participants: 110 patients with VIN: primary imiquimod:55; surgery:55 Inclusion criteria: Histologically confirmed VIN; visible measurable lesion; age =18 years; contraception (for premenopausal women); informed consent Exclusion criteria: Evidence of invasion; history of cancer or inflammatory dermatosis of the vulva; pregnancy; lactation; immunodeficiency; any treatment for VIN within the previous month; known hypersensitivity to imiquimod Treatment: Primary imiquimod group: patient self-administered, local application (slow escalating regime), for a period of 4 months (possible extension to 6 months). Dose reduction in case of severe side-effects Surgery group: decision on type of surgery (excision or ablation) based on clinical findings, surgeons recommendations, and patients preference Primary Outcome: Complete clinical response at 6 months after treatment start Secondary outcomes: Clinical response (complete and partial): change in lesion size in cm. Histologic response Amount and extent of surgical interventions for VIN Local HPV clearance Immune cells in the epidermis Aesthetic result (photo documentation) Health-related quality of life: questionnaires, study diary, VAS Long-term recurrence rate Statistics: Non-inferiority-trial. Analysis as intention-to-treat and per-protocol Time-plan: Active recruitment: 24 months Randomised controlled trial: 6 months Controlled short-term follow-up: 6 months Long-term follow-up: 5 years

The recruitment of the PITVIN Study has been extended and the study is still ongoing. Therefore no final reports can be submitted at this stage. The PITVIN study aims to evaluate the clinical management of HPV related high-grade squamous intraepithelial lesion (HSIL Vulva / VIN II and III). The multicentre prospective, randomized, unblinded trial compares primary treatment with the topical immune response modifier Imiquimod (Aldara) with the standard treatment (surgery). Main study outcome is the rate of clinical remission at 6 months. In addition, histologic remission, local HPV clearance, amount and extent of surgical procedures, immune cells in the epidermis and health-related quality of life, including sexuality, are investigated.The study aims to include 110 patients and nine study centres within Austria are involved in patient recruitment. Recruitment has been slower than expected, and so far only 54 patients could be included in the study. The majority of study participants was recruited by the principal investigator in the study centre Graz (45 patients) 9 patients were recruited by the other study centres. During investigator meetings the following factors were identified as possible obstacles to study recruitment: the rareness of the disease, unwillingness of patients to participate, lack of clinical time for recruitment. Due to the importance of the expected clinical results, study recruitment has been extended for at least another year. The combination of clinical data with histologic, immunologic, infectious and psychosexual parameters will give valuable information about the various aspects of VIN and its treatment.. The results from this study will help to guide clinical practice with level I evidence and allow for effective treatment with regard to clinical symptoms and patient needs.During the entire study period no suspected unexpected serious adverse reactions (SUSARs) have occurred. The study has been conducted according to study plan with good overall patient satisfaction.