Clinical Trial Evaluating Secondary HPV Vaccination After Treatment of High-grade Cervical Lesions (HPV2-2303)

Phase 2

Recruiting

• Conditions: Cervical Lesion
• Interventions: Biological: Human Papillomavirus 9-valent Vaccine, Recombinant

• Registration Number: NCT06658405
• Lead Sponsor: Centre Oscar Lambret

Brief Summary

This is a single-center, Phase II interventional study evaluating secondary HPV vaccination after treatment of high-grade cervical lesions. The study aims to estimate the rate of HPV clearance within two years following an initial positive HPV control test in women over 45 years of age who are chronic HPV carriers and have undergone treatment for high-grade intraepithelial cervical lesions, and who receive HPV vaccination.

The study includes two cohorts:

1. Eligible patients who consent to vaccination will participate in a prospective, single-center, single-arm, interventional clinical trial (Category 2).

2. Non-vaccinated patients will be included in a non-interventional observational study, with no changes to their standard care.

Detailed Description

The aim of this study is to estimate the proportion of HPV clearance within two years following an initial positive HPV control test in women over 45 years old who are chronic HPV carriers and have undergone treatment for high-grade intraepithelial cervical lesions. These women will receive HPV vaccination as part of the study.

Other objectives of the study include:

1. Describing the dynamics of viral clearance in chronic HPV carriers who receive HPV vaccination.

2. Evaluating the safety of HPV vaccination.

3. Estimating the incidence of recurrence of high-grade intraepithelial cervical lesions in chronic HPV carriers after surgical treatment of the initial lesion and HPV vaccination.

4. Estimating the incidence of invasive gynecological cancers (cervical, vaginal, or vulvar) in chronic HPV carriers after surgical treatment of the initial lesion and HPV vaccination.

5. Identifying factors associated with the refusal of HPV vaccination, such as smoking, parity, body mass index, employment status, education level, family history, and marital status.

6. Describing compliance with the proposed vaccination schedule in terms of:

1. Number of injections completed.

2. Adherence to the timing of injections.

7. Evaluating the effect of vaccination on:

1. HPV clearance within two years.

2. The dynamics of viral clearance.

3. The risk of recurrence of high-grade intraepithelial lesions.

4. The risk of developing invasive gynecological cancers (cervical, vaginal, or vulvar).

by comparing vaccinated patients included in the clinical trial with the cohort of non-vaccinated patients (those who refused HPV vaccination or for other reasons).

Study Timeline

• Study First Submitted: 2024-10-22
• Study First Submitted QC: 2024-10-23
• Study First Posted: 2024-10-26
• Study Start: 2025-01-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Primary Completion: 2028-10
• Study Completion: 2031-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 85

Inclusion Criteria

1. Common eligibility criteria for the study (for both cohorts) :

   1. Female patient over 45 years old
   2. Patient treated by conization for high-grade cervical epithelial lesion
   3. Positive HPV test at the 6-month post-operative control (a delay of 6 to 12 months will be accepted), leading to an indication for a control colposcopy (+/- biopsy) according to standard surveillance practices.
   4. N.B. : Patients with abnormalities at the initial control colposcopy and/or positive biopsy remain eligible for the study, whether vaccinated or not.

2. Additional eligibility criteria for the clinical trial (Vaccinated patients cohort)

   1. No contraindication to HPV vaccination with Gardasil 9
   2. Patient consented to HPV vaccination with Gardasil 9
   3. Affiliated with a social security system
   4. Informed and signed written consent provided
   5. N.B. : Patients infected with HIV are eligible for the vaccine trial provided they are on antiretroviral therapy.

3. Inclusion criteria for the data study (Non-vaccinated patients cohort)

   1. Patient eligible for the study (a) and not eligible for the clinical trial (b) due to:

      • refusal of vaccination, or
      • A contraindication to vaccination

   2. No objection to the use of their personal data for research purposes

N.B. : A patient who initially refused vaccination may later request to be vaccinated as part of the trial after signing the consent form. The vaccine trial analysis will include all patients who started vaccination within 6 months after the initial HPV control test.

Exclusion Criteria

1. Common exclusion criteria for the study (for both cohorts)

   1. History of primary HPV vaccination
   2. History of HPV-induced invasive cancer (cervical, vaginal, vulvar, anal, oropharyngeal cancer)

2. Exclusion criteria for the clinical trial (Vaccinated patients cohort)

   1. Patient refusing HPV vaccination
   2. Patient with a contraindication to HPV vaccination with Gardasil 9
   3. Patient deprived of liberty or under guardianship

3. Exclusion criteria for the data study (Non-vaccinated patients cohort) a) Opposition to the use of their personal data for research purposes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaccinated patients	Human Papillomavirus 9-valent Vaccine, Recombinant	Human papillomavirus vaccine, nonvalent, Gardasil 9

Primary Outcome Measures

Name	Time	Method
Proportion of HPV-negative status	Within 2 years after the initial HPV control test	The primary outcome is to estimate the proportion of HPV-negativation status within two years of the initial positive HPV control test. Negativation is defined as a negative HPV test result. If the patient cannot be evaluated due to the occurrence of cancer, this will be considered a failure (equivalent to absence of negativation).

Secondary Outcome Measures

Name	Time	Method
Dynamics of HPV viral clearance	every 12 months for up to 5 years	HPV status over time assessed by smear every 12 months until HPV-negative status (in the study: within 5 years of follow-up). When the test is negative, a follow-up smear is performed three years later (in the study: within 5 years of follow-up)
Adverse Events	Throughout the vaccination schedule plus 30 days	Adverse events will be recorded and evaluated according to the NCI-CTCAE V5.0 scale. AEs will be documented after each vaccination, during subsequent injections, and through a follow-up phone call 30 days after the third injection. Severe Adverse Events (grade ≥3) will be considered significant.
Incidence of high-grade intraepithelial lesions	From the initial HPV control test up to the first recurrence event up to 5 years	The time to recurrence of high-grade cervical lesions will be calculated from the date of the initial HPV control test to the first documented event of lesion recurrence, as indicated by clinical follow-up and diagnostic testing.
Incidence of invasive gynecological cancer	From the initial HPV control test to the occurrence of invasive cancer up to 5 years	The incidence of invasive gynecological cancers (cervix, vagina, vulva) will be determined by calculating the time from the initial HPV control test to the first occurrence of HPV-related invasive cancer at any sites (cervix, vagina, vulva)
Compliance with vaccination schedule	Throughout the vaccination period (up to 1 year)	Compliance will be measured by the number of vaccine doses received and adherence to the recommended timing between injections, including the interval between the 1st and 3rd doses of Gardasil 9.

Trial Locations

Locations (1)

Centre Oscar Lambret; 🇫🇷 Lille, France