Evaluation of New Diagnostic Tool Using Fluorescence to Detect High-grade Vulvar Intraepithelial Neoplasia (PhotodiVIN)

Evaluation of the Ability of PpIX Fluorescence to Mark High-grade Vulvar Intraepithelial Neoplasia Following the Methyl Aminolevulinate (Metvixia®) Application

This study is a single-center propsective clinical trial to assess the ability of fluorescence techniques to mark high-grade vulvar intraepithelial neoplasias including high-grade vulvar squamous intraepithelial lesions and differentiated vulvar intraepithelial neoplasias following 3 hours Metvixia application.

Study Overview

• Status: Recruiting
• Conditions: Vulvar Intraepithelial Neoplasia; Vulvar High Grade Squamous Intraepithelial Lesion; Differentiated Vulvar Intraepithelial Neoplasia
• Intervention / Treatment: Drug: Metvixia Topical Cream

• Study Type: Interventional
• Enrollment (Estimated): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Priscillia TOSTI; Phone Number: 00 33 383 598 657; Email: p.tosti@nancy.unicancer.fr
• Study Contact Backup: Name: Naoual Boujedaini, PhD; Phone Number: 00 33 383 598 668; Email: n.boujedaini@nancy.unicancer.fr

Study Locations

• France
  • Vandœuvre-lès-Nancy, France, 54506
    • Recruiting
    • Institut de Cancérologie de Lorraine
    • Contact: BOUJEDAINI Naoual, PhD; Phone Number: +33 (0)3 83 59 86 68; Email: n.boujedaini@nancy.unicancer.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged 18 and over,
• With isolated high-grade vulvar intraepithelial neoplasia OR associated with invasive cancer proven histologically by biopsy
• Naive of any vulvovaginal treatment (surgery or radiotherapy)
• No metastases
• WHO <or equal to 3
• Contraception method for women of childbearing potential
• Patient affiliated to the social security scheme
• Patient who understood, signed and dated the information note and the
• consent form,
• Patient able and willing to follow all study procedures in accordance with the protocol.

Exclusion Criteria:

• History of hypersensitivity to the active substance methyl aminolevulinate or to any of the components of the drug (including peanut oil and refined almond oil), soybean or peanut
• Ulceration or hyperpigmented lesions of the vulva
• Patient with porphyria
• Any previous vulvovaginal treatment (surgery or radiotherapy)
• Metastatic disease
• Patient undergoing treatment for any other invasive cancer
• Pregnant, likely to be or breastfeeding patient
• Patient deprived of liberty or under guardianship (including guardianship)
• Inability to undergo medical monitoring of the trial for geographic, social or psychological reasons.
• Patient already included in another therapeutic trial with an experimental molecule,
• Associated pathology that may prevent the patient from receiving METVIXIA application and light exposure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Metvixia application for Photodynamic diagnosis; Patients who benefit Metvixia application to the vulva to realize fluorescence guided biopsies (Photodynamic diagnosis).

Drug: Metvixia Topical Cream; Metvixia is applied with a spatula, in a thick layer, to clinically visible lesions and all over the vulva. After applying the cream, the area will be covered with a bandage which should remain in place for 3 hours. After 3 hours of application, the bandage and the cream will be carefully removed. The application area will be cleaned and then immediately exposed to a continuous spectrum of light at a wavelength of 405 nm by a xenon lamp. The most fluorescent areas will be identified. Then in white light, the practitioner will perform at least two biopsies under non-topical local anesthesia in the area of application of Metvixia®: one in the fluorescent area and one in the non-fluorescent area. If there is no fluorescent labeling, two samples will be taken from two different non-fluorescent areas. In the event that all the zone is fluorescent , two samples will be taken from two different fluorescent zones.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the success of the photodynamic diagnosis	Percentage of patients for whom the procedure successfully demonstrated high-grade vulvar intraepithelial neoplasias in fluorescence confirmed by biopsy. A patient will be considered successful if the presence or absence of fluorescence is consistent with the anatomo-pathological result, that means if her sample in the fluorescent area is positive in pathology and her sample in the non-fluorescent area is negative in anatomo-pathology. For a patient with no fluorescent labeling, the pathological results of her two samples must be negative for the patient to be considered successful. For a patient where the entire area fluoresces, the anatomo-pathological result of her two samples must be positive for the patient to be considered successful.	14 days (+/- 4 days) after the photodiagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the photodynamic diagnosis	The sensitivity will correspond to the number of fluorescent zones among the positive zones in anatomopathology.	14 days (+/- 4 days) after the photodiagnosis
Specifity of the photodynamic diagnosis	The specificity will correspond to the number of non-fluorescent zones among the negative zones in anatomo-pathology.	14 days (+/- 4 days) after the photodiagnosis
Intensity of flurescence evaluation	The fluorescence intensity will be measured by the signal to noise ratio, also called SNR (Signal to Noise Ratio) on photographie	The day of the photo analysis with a specific software
Tolerance evaluation	The tolerance of the application will be assessed by the number of grade 3 to 5 toxicity. The toxicity will be evaluated using the CTCAE v5 scale (Common Terminology for Adverse Events). The different grade on this scale is 1 to 5 (1 correspond to a asymptomatic or mild symptome, 2 to moderate toxicity, 3 to severe or medically significant but not immediately life-threatening toxicity, 4 to life-threatening consequences or urgent intervention indicated and 5 to the death related to the toxicity.	At inclusion, after applying the cream for 3 hours, before and immediately after the blue light exposition and at and the final study visite (14 days +/- 4 after the photodiagnosis)
Pain Evaluation	Pain will be assessed using a numerical scale from 0 to 10 (0 corresponds to no pain and 10 to maximum pain)	At inclusion, 1 hour after Metvixia application, before and immediately after the blue light exposition and at and the final study visite (14 days +/- 4 after the inclusion)

Collaborators and Investigators

• Sponsor: Institut de Cancérologie de Lorraine
• Investigators: Principal Investigator: Lorraine HEJL, MD, Institut de Cancérologie de Lorraine

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Estimated): December 17, 2024
• Study Completion (Estimated): December 17, 2024

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: October 22, 2021
• First Posted (Actual): November 2, 2021

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Vulvar Intraepithelial Neoplasia; Vulvar High Grade Squamous Intraepithelial Lesion; Photodynamic diagnosis; Metvixia; Differentiated vulvar intraepithelial neoplasia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Neoplasms, Squamous Cell; Uterine Cervical Dysplasia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Squamous Intraepithelial Lesions of the Cervix; Photosensitizing Agents; Dermatologic Agents; Methyl 5-aminolevulinate
• Other Study ID Numbers: 2021-000568-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No