In this trial, the efficacy of Gardasil combined with imiquimod in women with usual type Vulvar Intraepithelial Neoplasia is investigated. MedDRA version: 9.1 Level: LLT Classification code 10047778 Term: Vulvar cancer in situ MedDRA version: 9.1 Level: LLT Classification code 10066416 Term: Vulvovaginal human papilloma virus infection MedDRA version: 9.1 Level: LLT Classification code 10046859 Term: Vaccination MedDRA version: 9.1 Level: LLT Classification code 10062059 Term: Histology abno
Conditions
Interventions
Trade Name: Gardasil
Pharmaceutical Form: Suspension for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use
Trade Name: Ald
Sponsors
Erasmus MC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Histological proven usual type VIN, without invasion -Previous treatment with imiquimod for 12-16 weeks with a partial response to imiquimod treatment defined as a reduction in lesion size of 26%-99% -The patient is willing to use a medically acceptable method of contraception throughout the study -Age 18 and above Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - (Micro-)invasive carcinoma - Pregnancy and/or breastfeeding - Past history of vulvar cancer - Differentiated (non HPV-related) VIN - Other treatment of VIN or anogenital warts within 1 month of start trial - Hypersensitivity to any components of the vaccine or cream formulation - History of psoriasis or other inflammatory dermatosis of the vulva - Immunodeficiency (e.g. HIV, systemic corticosteroid use) - Insufficient understanding of the Dutch language - Partial responders who are disease-free at study-entry due to other treatment of VIN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.Evaluation of efficacy of the following two treatments for usual type VIN: -Vaccination + imiquimod: Vaccination with Gradasil, followed by local applications of imiquimod 5% cream. -Imiquimod alone: Placebo vaccination (saline) followed by local applications of imiquimod 5% cream. 2.Evaluation of the systemic and local immunological response to both treatments. 3.Evaluation of the effect of treatments on HPV DNA presence in VIN lesions, by comparison of Polymerase Chain Reaction (PCR) HPV-DNA detection in vulvar biopsies taken at 0 and 36 weeks. ;Secondary Objective: -Evaluation of effect of vaccination against HPV types 16, 18, 6 and 11 by measuring the antibody titres (against types 16, 18, 6 and 11) at 0, 8, 16, 24 and 36 weeks. -Evaluation of quality of life as measured by quality of life questionnaire at 0 and 36 weeks. ;Primary end point(s): Clinical response to the treatment in VIN lesions after the end of imiquimod treatment and the last vaccination, measured by 1) reduction in lesion size, 2) histological regression of usual type VIN to ‘normal’ vulvar tissue and 3) relieve of symptoms. Other main study parameters are absence of HPV DNA in the original VIN lesions after treatment, normalization of immunocompetent cell counts and production of cytokines in peripheral blood and by Peripheral Blood Mononuclear Cells (PBMCs). Secondary study parameters include presence of antibody titres against HPV 16,18, 6, and 11 and improvement of quality of life. | — |
Countries
Netherlands
Outcome results
None listed