History of Changes for Study: NCT01861535

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

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Study Record Versions

Version	Submitted Date	Changes
1	May 21, 2013	None (earliest Version on record)
2	June 7, 2013	Recruitment Status, Study Status, Contacts/Locations and Oversight
3	June 4, 2014	Contacts/Locations and Study Status
4	April 9, 2015	Arms and Interventions, Study Status and Contacts/Locations
5	January 12, 2016	Study Status and Study Description
6	August 16, 2016	Study Status
7	March 28, 2018	Study Status
8	May 13, 2019	Study Status
9	January 10, 2020	Recruitment Status, Study Status, Contacts/Locations and Study Design
10	September 11, 2020	Study Status
11	January 21, 2021	Study Status
12	April 13, 2021	Recruitment Status and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	KLI293
Brief Title:	Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia (PITVIN)
Official Title:	Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia
Secondary IDs:

Study Status


Record Verification:	May 2013
Overall Status:	Not yet recruiting
Study Start:	June 2013
Primary Completion:	June 2016 [Anticipated]
Study Completion:	September 2016 [Anticipated]

First Submitted:	May 6, 2013
First Submitted that Met QC Criteria:	May 21, 2013
First Posted:	May 23, 2013 [Estimate]

Last Update Submitted that Met QC Criteria:	May 21, 2013
Last Update Posted:	May 23, 2013 [Estimate]

Sponsor/Collaborators


Sponsor:	Medical University of Graz
Responsible Party:	Sponsor
Collaborators:	Austrian Science Fund (FWF)

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	Yes

Study Description


Brief Summary:	The purpose of this study is to evaluate the efficacy, defined as complete clinical response 6 months after treatment start, of Imiquimod compared to the standard treatment (surgery) for vulvar intraepithelial neoplasia (VIN).
Detailed Description:

Conditions


Conditions:	Vulvar Intraepithelial Neoplasia
Keywords:	VIN Imiquimod Surgery HPV Patient satisfaction

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	110 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

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:

Aldara

Procedure: Surgery

Other Names:

Excision
Ablation

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:

Excision
Ablation

Outcome Measures


Primary Outcome Measures:
1.	Complete clinical response [ Time Frame: 6 months ] No clinical evidence of vulvar lesion, i.e. 100% reduction of primary lesion size
Secondary Outcome Measures:
1.	Clinical response/ lesion size [ Time Frame: 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).
2.	Histologic response [ Time Frame: 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
3.	Extent of surgery [ Time Frame: 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)
4.	HPV status [ Time Frame: 6 months ] HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.
5.	Clinical response/lesion size [ Time Frame: 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).
6.	Extent of surgery [ Time Frame: 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)
7.	HPV status [ Time Frame: 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:
1.	"Cervical Dysplasia Distress" Questionnaire [ Time Frame: 6 months ] Change from baseline in "Cervical Dysplasia Distress" score at 6 months
2.	"Cervical Dysplasia Distress" questionnaire [ Time Frame: 12 months ] Change from Baseline in "Cervical Dysplasia Distress" score at 12 months
3.	"Fear of Progression" Questionnaire [ Time Frame: 6 months ] Change from Baseline "Fear of Progression" score at 6 months.
4.	"Fear of Progression" questionnaire [ Time Frame: 12 months ] Change from Baseline "Fear of Progression" score at 12 months.
5.	"Sexual activity" Questionnaire [ Time Frame: 6 months ] Change from baseline "Sexual activity" score at 6 months
6.	"Sexual activity" questionnaire [ Time Frame: 12 months ] Change from baseline "Sexual activity" score at 12 months
7.	Immune cells in the epidermis [ Time Frame: 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.
8.	Aesthetic results [ Time Frame: 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.
9.	Aesthetic results [ Time Frame: 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.
10.	Visual analogue scale (VAS) for assessment of pain and pruritus [ Time Frame: 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


Minimum Age:	18 Years
Maximum Age:	90 Years
Sex:	Female
Gender Based:
Accepts Healthy Volunteers:	No
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/Locations


Central Contact Person:	Gerda Trutnovsky, MD Telephone: +43 316 385 Ext. 81081 Email: gerda.trutnovsky@medunigraz.at
Study Officials:	Gerda Trutnovsky, MD Principal Investigator Medical University of Graz
	Karl Tamussino, MD Study Director Medical University of Graz
Locations:	Austria
	Department of Obstetrics and Gynecology/ Medical University of Graz Graz, Austria, 8036 Contact:Contact: Gerda Trutnovsky, MD +43 316 385 Ext. 81081 gerda.trutnovsky@medunigraz.at Contact:Contact: Olaf Reich, MD +43 316 385 Ext. 81616 olaf.reich@medunigraz.at Contact:Principal Investigator: Gerda Trutnovsky, MD
	Department of Gynecology and Obstetrics, Medical University of Innsbruck Innsbruck, Austria, 6020 Contact:Contact: Andreas Widschendter, MD +43 50 504 Ext. 23055 andreas.widschwendter@i-med.ac.at Contact:Principal Investigator: Andreas Widschwendter, MD
	Department of General Gynecology and Gynecology Oncology, Medical University of Vienna Vienna, Austria, 1090 Contact:Contact: Elmar Joura, MD +43 1 40400 Ext. 2915 elmar.joura@meduniwien.ac.at Contact:Contact: Christoph Grimm, MD +43 316 40400 Contact:Principal Investigator: Elmar Joura, MD

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