Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL

NCT06052696 | Not Yet Recruiting Phase 4

• 2 other identifiers: MEC-2023-05262023-506792-94-00
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Problem description: Yearly, approximately 45000 women develop vulvar cancer worldwide. It is estimated that about 30% of all vulvar carcinomas are HPV related. As with other HPV related (pre)malignancies, the incidence has been rising over the past 20 years. The peak incidence of premalignant lesions of the vulva, also called Vulvar High Grade Squamous Intraepithelial Lesion (vHSIL), lies between 35 and 40 years of age. Multiple treatments are available, including surgery, laser vaporization, and topical imiquimod, with comparable success rate. Despite treatment, at least 30% of women will develop a recurrence within 2 years, with a much higher lifetime risk of recurrence. This results in multiple treatments with sometimes disfiguring effects and associated negative psychosocial and psychosexual impact. Woman with vulvar HSIL have a lifelong increased risk of vulvar cancer, and approximately 10% of women with (treated) vulvar HSIL will develop vulvar cancer within 10 years of first diagnosis. The risk of malignancy is significantly higher in women with recurrent disease, compared to women without recurrence. Solution / research direction, To date, a successful strategy for reduction of recurrences of HSIL has not been established. The available positive evidence on the use of concurrent HPV vaccination in the treatment of vulvar HSIL is rising, yet insufficient to guide clinical practice. There is limited data that prophylactic HPV vaccination after treatment of vulvar HSIL reduces the chance of recurrence, therefore leading to a reduction in repeated (surgical) interventions. There are no randomised controlled studies supporting this data. Aim The aim of current project is to determine the effectiveness of nonavalent HPV vaccination versus placebo in preventing recurrence in women treated for vulvar HSIL. Plan of investigation This is a randomised, double blinded, placebo controlled trial in women treated for vulvar HSIL. Adult female patients, diagnosed with vulvar HSIL planned for treatment and no prior HPV vaccination will be included. Randomisation will be in a 1:1 ratio to additional nonavalent HPV vaccination versus additional placebo vaccination. Expected outcome. Based on previous non-randomised studies, a significant reduction in recurrences, improvement of quality of life and a reduction of economic burden of the disease is expected.

Conditions

Vulvar HSIL; HPV

Keywords

HPV; VHSIL; Vaccination

Outcome Measures

Primary Outcomes (1)

• Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo?

  Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months

  24 months after last inclusion

Secondary Outcomes (11)

• 1. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months?

  6 and 12 months after last inclusion

• 2. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months in primary episode vHSIL versus recurrence?

  6 and 12 months after last inclusion

• 3. What is the effectiveness of adjuvant vaccination in different treatments of vHSIL (laser, imiquimod, excision) at 24 months?

  24 months after last inclusion

• 4. How often is additional treatment for vHSIL needed in the study period? Is this different between the study groups?

  24 months after last inclusion

• 5. What is the effect of vaccination versus placebo on different HPV types (HPV type of primary and recurrence)?

  24 months after last inclusion

Study Arms (2)

Gardasil 9

EXPERIMENTAL

see intervention

Drug: Gardasil 9 Suspension for Injection

placebo

PLACEBO COMPARATOR

see intervention

Drug: Placebo

Interventions

Gardasil 9 Suspension for Injection DRUG

After randomisation in the Gardasil arm, women will receive 3 Gardasil vaccinations 1. First injection: preferable at time of start treatment (imiquimod, lase or surgery). Window 4 weeks prior to treatment start (because surgical treatment can be postponed for logistical reasons) and 4 weeks after start treatment. 2. Second injection: should be administered at least 1 month after the first injection and 3 months before the third injection. 3. Third injection should be administered at 3 months after second injection. All injections should be administered within 1 year.

Gardasil 9

Placebo DRUG

After randomisation in the PLacebo arm, women will receive 3 Placebo vaccination with NaCl 0.9% 1. First injection: preferable at time of start treatment (imiquimod, lase or surgery). Window 4 weeks prior to treatment start (because surgical treatment can be postponed for logistical reasons) and 4 weeks after start treatment. 2. Second injection: should be administered at least 1 month after the first injection and 3 months before the third injection. 3. Third injection should be administered at 3 months after second injection. All injections should be administered within 1 year.

placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women 18 years or older
• Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL), histologically proven
• Planned for treatment (surgical, laser or imiquimod) for vHSIL

You may not qualify if:

• Prior HPV vaccination
• (Micro-) invasive carcinoma or history of HPV related genital carcinoma (cervix, anal, vulva)
• Pregnancy
• Women allergic to vaccine components
• HIV infection
• Immune compromised patients (currently on immunosuppressive medication

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, Netherlands

Location

Related Publications (1)

• Vaessen VJGM, van de Laar RLO, Piso-Jozwiak M, Dalm VASH, Joura EA, Jentschke M, van Beekhuizen HJ. Adjuvant nonavalent HPV vaccination in women treated for vulvar HSIL, a randomized placebo-controlled trial; VulVaccin study protocol. BMC Cancer. 2025 May 20;25(1):903. doi: 10.1186/s12885-025-14275-w.

  PMID: 40394508 DERIVED

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, gynaecologic oncologist.

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 25, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 25, 2023

Record last verified: 2023-09

Locations

NL (1)