PITVIN: Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Primary Imiquimod 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
Other Names:
|
| Active Comparator: Primary surgery 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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Complete clinical response [6 months]
No clinical evidence of vulvar lesion, i.e. 100% reduction of primary lesion size
Secondary Outcome Measures
- Clinical response/ lesion size [6 months]
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).
- Histologic response [6 months]
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
- Extent of surgery [6 months]
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)
- HPV status [6 months]
HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.
- Clinical response/lesion size [12 months]
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).
- Extent of surgery [12 months]
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)
- HPV status [12 months]
HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.
Other Outcome Measures
- "Cervical Dysplasia Distress" Questionnaire [6 months]
Change from baseline in "Cervical Dysplasia Distress" score at 6 months
- "Cervical Dysplasia Distress" questionnaire [12 months]
Change from Baseline in "Cervical Dysplasia Distress" score at 12 months
- "Fear of Progression" Questionnaire [6 months]
Change from Baseline "Fear of Progression" score at 6 months.
- "Fear of Progression" questionnaire [12 months]
Change from Baseline "Fear of Progression" score at 12 months.
- "Sexual activity" Questionnaire [6 months]
Change from baseline "Sexual activity" score at 6 months
- "Sexual activity" questionnaire [12 months]
Change from baseline "Sexual activity" score at 12 months
- Immune cells in the epidermis [6 months]
Histochemical analysis of immune cells from vulvar biopsy samples will be performed at baseline and at 6 months. Frozen sections will be prepared and stained with corresponding cell markers. Immune cell populations will be quantified as number of cells per square millimetre and will be compared between the two treatment groups. The following markers and their primary antibodies will be analysed: CD1a, marker for Langerhans cells, CD94, marker for natural killer cells, CD4, marker for T-helper cells, CD8, marker for cytotoxic T-cells and CD207, marker for immature dendritic cells expressing Langerin.
- Aesthetic results [6 months]
Detailed photos of the overall vulva will be taken. Photos will be compared to photos taken at baseline and judged by 4 independent, blinded observers for aesthetic results.
- Aesthetic results [12 months]
Detailed photos of the overall vulva will be taken. Photos will be compared to photos at baseline and judged by 4 independent, blinded observers for aesthetic results.
- Visual analogue scale (VAS) for assessment of pain and pruritus [6 months]
Change of VAS score for pain and pruritus from baseline to 6 months. VAS will be assessed at baseline, 1,2 ,3,4,5 and 6 months.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dep. of Gynecology and Obstetrics, Landes Frauen- und Kinderklinik Linz | Linz | Oberösterreich | Austria | 4020 |
| 2 | Dep. of Gynecology, Krankenhaus Barmherzige Brüder Graz | Graz | Styria | Austria | 8020 |
| 3 | Department of Obstetrics and Gynecology/ Medical University of Graz | Graz | Austria | 8036 | |
| 4 | Department of Gynecology and Obstetrics, Medical University of Innsbruck | Innsbruck | Austria | 6020 | |
| 5 | Dep. of Gynecology and Obstetrics, Klinikum Klagenfurt | Klagenfurt | Austria | ||
| 6 | Dep. of Gynecology and Obstetrics | Leoben | Austria | ||
| 7 | Dep. of Gynecology, Krankenhaus Barmherzige Schwestern Linz | Linz | Austria | 4010 | |
| 8 | Dep. of Gynecology and Obstetrics, Landeskrankenhaus Salzburg | Salzburg | Austria | 5020 | |
| 9 | Department of General Gynecology and Gynecology Oncology, Medical University of Vienna | Vienna | Austria | 1090 |
Sponsors and Collaborators
- Medical University of Graz
- Austrian Science Fund (FWF)
Investigators
- Principal Investigator: Gerda Trutnovsky, MD, Medical University of Graz
- Study Director: Karl Tamussino, MD, Medical University of Graz
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KLI293