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Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia (PITVIN)

Primary Purpose

Vulvar Intraepithelial Neoplasia

Status
Completed
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
Imiquimod
Surgery
Sponsored by
Medical University of Graz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vulvar Intraepithelial Neoplasia focused on measuring VIN, Imiquimod, Surgery, HPV, Patient satisfaction

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Dep. of Gynecology and Obstetrics, Landes Frauen- und Kinderklinik Linz
  • Dep. of Gynecology, Krankenhaus Barmherzige Brüder Graz
  • Department of Obstetrics and Gynecology/ Medical University of Graz
  • Department of Gynecology and Obstetrics, Medical University of Innsbruck
  • Dep. of Gynecology and Obstetrics, Klinikum Klagenfurt
  • Dep. of Gynecology and Obstetrics
  • Dep. of Gynecology, Krankenhaus Barmherzige Schwestern Linz
  • Dep. of Gynecology and Obstetrics, Landeskrankenhaus Salzburg
  • Department of General Gynecology and Gynecology Oncology, Medical University of Vienna

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Primary Imiquimod

Primary surgery

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Complete clinical response
No clinical evidence of vulvar lesion, i.e. 100% reduction of primary lesion size

Secondary Outcome Measures

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).
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
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)
HPV status
HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.
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).
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)
HPV status
HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.

Full Information

First Posted
May 6, 2013
Last Updated
April 13, 2021
Sponsor
Medical University of Graz
Collaborators
Austrian Science Fund (FWF)
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1. Study Identification

Unique Protocol Identification Number
NCT01861535
Brief Title
Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia
Acronym
PITVIN
Official Title
Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
February 2021 (Actual)
Study Completion Date
February 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Graz
Collaborators
Austrian Science Fund (FWF)

4. Oversight

Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vulvar Intraepithelial Neoplasia
Keywords
VIN, Imiquimod, Surgery, HPV, Patient satisfaction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Primary Imiquimod
Arm Type
Experimental
Arm Description
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
Arm Title
Primary surgery
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Imiquimod
Other Intervention Name(s)
Aldara
Intervention Type
Procedure
Intervention Name(s)
Surgery
Other Intervention Name(s)
Excision, Ablation
Primary Outcome Measure Information:
Title
Complete clinical response
Description
No clinical evidence of vulvar lesion, i.e. 100% reduction of primary lesion size
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Clinical response/ lesion size
Description
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).
Time Frame
6 months
Title
Histologic response
Description
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
Time Frame
6 months
Title
Extent of surgery
Description
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)
Time Frame
6 months
Title
HPV status
Description
HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.
Time Frame
6 months
Title
Clinical response/lesion size
Description
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).
Time Frame
12 months
Title
Extent of surgery
Description
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)
Time Frame
12 months
Title
HPV status
Description
HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
"Cervical Dysplasia Distress" Questionnaire
Description
Change from baseline in "Cervical Dysplasia Distress" score at 6 months
Time Frame
6 months
Title
"Cervical Dysplasia Distress" questionnaire
Description
Change from Baseline in "Cervical Dysplasia Distress" score at 12 months
Time Frame
12 months
Title
"Fear of Progression" Questionnaire
Description
Change from Baseline "Fear of Progression" score at 6 months.
Time Frame
6 months
Title
"Fear of Progression" questionnaire
Description
Change from Baseline "Fear of Progression" score at 12 months.
Time Frame
12 months
Title
"Sexual activity" Questionnaire
Description
Change from baseline "Sexual activity" score at 6 months
Time Frame
6 months
Title
"Sexual activity" questionnaire
Description
Change from baseline "Sexual activity" score at 12 months
Time Frame
12 months
Title
Immune cells in the epidermis
Description
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.
Time Frame
6 months
Title
Aesthetic results
Description
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.
Time Frame
6 months
Title
Aesthetic results
Description
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.
Time Frame
12 months
Title
Visual analogue scale (VAS) for assessment of pain and pruritus
Description
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.
Time Frame
6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerda Trutnovsky, MD
Organizational Affiliation
Medical University of Graz
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Karl Tamussino, MD
Organizational Affiliation
Medical University of Graz
Official's Role
Study Director
Facility Information:
Facility Name
Dep. of Gynecology and Obstetrics, Landes Frauen- und Kinderklinik Linz
City
Linz
State/Province
Oberösterreich
ZIP/Postal Code
4020
Country
Austria
Facility Name
Dep. of Gynecology, Krankenhaus Barmherzige Brüder Graz
City
Graz
State/Province
Styria
ZIP/Postal Code
8020
Country
Austria
Facility Name
Department of Obstetrics and Gynecology/ Medical University of Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Department of Gynecology and Obstetrics, Medical University of Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Dep. of Gynecology and Obstetrics, Klinikum Klagenfurt
City
Klagenfurt
Country
Austria
Facility Name
Dep. of Gynecology and Obstetrics
City
Leoben
Country
Austria
Facility Name
Dep. of Gynecology, Krankenhaus Barmherzige Schwestern Linz
City
Linz
ZIP/Postal Code
4010
Country
Austria
Facility Name
Dep. of Gynecology and Obstetrics, Landeskrankenhaus Salzburg
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Department of General Gynecology and Gynecology Oncology, Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria

12. IPD Sharing Statement

Citations:
PubMed Identifier
35483400
Citation
Trutnovsky G, Reich O, Joura EA, Holter M, Ciresa-Konig A, Widschwendter A, Schauer C, Bogner G, Jan Z, Boandl A, Kalteis MS, Regauer S, Tamussino K. Topical imiquimod versus surgery for vulvar intraepithelial neoplasia: a multicentre, randomised, phase 3, non-inferiority trial. Lancet. 2022 May 7;399(10337):1790-1798. doi: 10.1016/S0140-6736(22)00469-X. Epub 2022 Apr 25. Erratum In: Lancet. 2022 Oct 8;400(10359):1194.
Results Reference
derived

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Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia

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