Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL

NCT ID: NCT06052696

Last Updated: 2023-09-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2030-12-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Gardasil 9

see intervention

Group Type: EXPERIMENTAL

Gardasil 9 Suspension for Injection

Intervention Type: 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.

placebo

see intervention

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

Gardasil 9 Suspension for Injection

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Dutch Cancer Society

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ralf van de Laar

MD, gynaecologic oncologist.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Erasmus MC

Rotterdam, , Netherlands

Countries

Netherlands

Facility Contacts

R. van de Laar

Role: primary

vulvaccin@erasmusmc.nl

References

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.

Reference Type: DERIVED

PMID: 40394508 (View on PubMed)

Other Identifiers

2023-506792-94-00

Identifier Type: OTHER

Identifier Source: secondary_id

MEC-2023-0526

Identifier Type: -

Identifier Source: org_study_id