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

• ClinicalTrials.gov Identifier: NCT01861535
• Recruitment Status: Completed
• First Posted: May 23, 2013
• Last Update Posted: April 14, 2021
• Sponsor: Medical University of Graz
• Collaborator: Austrian Science Fund (FWF)
• Information provided by (Responsible Party): Medical University of Graz

Tracking Information

• First Submitted Date: May 6, 2013
• First Posted Date: May 23, 2013
• Last Update Posted Date: April 14, 2021
• Study Start Date: June 2013
• Actual Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2013)

Complete clinical response [ Time Frame: 6 months ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 21, 2013)

• 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).
• 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
• 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)
• 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.
• 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).
• 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)
• 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 21, 2013)

• "Cervical Dysplasia Distress" Questionnaire [ Time Frame: 6 months ]
  Change from baseline in "Cervical Dysplasia Distress" score at 6 months
• "Cervical Dysplasia Distress" questionnaire [ Time Frame: 12 months ]
  Change from Baseline in "Cervical Dysplasia Distress" score at 12 months
• "Fear of Progression" Questionnaire [ Time Frame: 6 months ]
  Change from Baseline "Fear of Progression" score at 6 months.
• "Fear of Progression" questionnaire [ Time Frame: 12 months ]
  Change from Baseline "Fear of Progression" score at 12 months.
• "Sexual activity" Questionnaire [ Time Frame: 6 months ]
  Change from baseline "Sexual activity" score at 6 months
• "Sexual activity" questionnaire [ Time Frame: 12 months ]
  Change from baseline "Sexual activity" score at 12 months
• 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.
• 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.
• 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.
• 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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia
• Official Title: Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Vulvar Intraepithelial Neoplasia

Intervention

• Drug: Imiquimod
  Other Name: Aldara
• Procedure: Surgery
  Other Names:

  • Excision
  • Ablation

Study Arms

• 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
  Intervention: Drug: Imiquimod
• 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.
  Intervention: Procedure: Surgery

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 21, 2013): 110
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 2021
• Actual Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT01861535
• Other Study ID Numbers: KLI293
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Medical University of Graz
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of Graz
• Original Study Sponsor: Same as current
• Collaborators: Austrian Science Fund (FWF)

Investigators

• Principal Investigator: Gerda Trutnovsky, MD; Medical University of Graz
• Study Director: Karl Tamussino, MD; Medical University of Graz

• PRS Account: Medical University of Graz
• Verification Date: April 2021