Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy (defined as complete clinical response at 6 months) of imiquimod vs. standard treatment (surgery) for vulvar intraepithelial neoplasia (VIN).

Official Title
-----------------
Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia

Conditions
-----------------
Vulvar Intraepithelial Neoplasia

Intervention / Treatment
-----------------
* Drug: Imiquimod
* Procedure: Surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed VIN (only usual type, formerly VIN 2-3) Visible, measurable lesion(s) Contraception (for premenopausal women) Exclusion Criteria: Evidence of invasion History of cancer or severe inflammatory dermatosis of the vulva Pregnancy, lactation Immunodeficiency Any treatment for VIN within the previous three months Known hypersensitivity to imiquimod

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary Imiquimod<br>Treatment with imiquimod will be patient self-administered for a period of 4 months with possible extension to 6 months. A thin layer of imiquimod cream should be applied to the lesion and remain overnight without a cover. Application will be once a week for 2 weeks, then twice a week the following 2 weeks and, if tolerated, 3 times a week for the last weeks. In case of severe side-effects the number of applications can be reduced; a treatment-free period of no more than 1 week is permitted | Drug: Imiquimod<br> <br> * Other names: Aldara;|
| Active Comparator: Primary surgery<br>The type of surgery (excision or ablation) will be based on clinical findings and surgeon's judgement. After excision the specimen will be histologically analyzed to assess resection margins and rule out invasion. | Procedure: Surgery<br> <br> * Other names: Ablation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical response | No clinical evidence of vulvar lesion, i.e. 100% reduction of primary lesion size | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response/ lesion size | Vulvar lesions will be described, measured with calipers, mapped and photographed. The digital photos will be analyzed with a computer program (ImageJ) to calculate the total lesion size in cm². Results will be classified as: no response (NR, reduction in lesion size of 25% or less), weak partial response (wPR, 26-75% reduction), strong partial response (stPR, 76%-99% reduction) and Complete response (CR, 100% reduction). | 6 months | 
| Histologic response | At baseline punch biopsies will be taken from the affected areas. The site of the initial biopsy will be photodocumented to ensure that the follow-up biopsy at 6 months is taken from the same site. Histologic results will be classified as response (R): complete disappearance of usual type VIN or reduction to VIN1,or no response (NR). All biopsy samples will be analysed independently by two experienced gynecologic pathologists unaware of the treatment allocation | 6 months | 
| Extent of surgery | The number, types and extent of surgical procedures will be recorded. The extent of surgery will be recorded as total operated lesion size (in cm², as measured on pre-operative photograph) and relative operated lesion size (percentage of operated lesion size compared with the original pretreatment lesion size) | 6 months | 
| HPV status | HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe. | 6 months | 
| Clinical response/lesion size | Vulvar lesions will be described, measured with calipers, mapped and photographed. The digital photos will be analyzed with a computer program (ImageJ) to calculate the total lesion size in cm². Results will be classified as: no response (NR, reduction in lesion size of 25% or less), weak partial response (wPR, 26-75% reduction), strong partial response (stPR, 76%-99% reduction) and Complete response (CR, 100% reduction). | 12 months | 
| Extent of surgery | The number, types and extent of surgical procedures will be recorded. The extent of surgery will be recorded as total operated lesion size (in cm², as measured on pre-operative photograph) and relative operated lesion size (percentage of operated lesion size compared with the original pretreatment lesion size) | 12 months | 
| HPV status | HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Imiquimod, Surgery, HPV, Patient satisfaction, VIN