Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL, a Randomised Placebo Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 2
- 主要终点
- Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo?
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women 18 years or older
- •Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL), histologically proven
- •Planned for treatment (surgical, laser or imiquimod) for vHSIL
排除标准
- •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
研究组 & 干预措施
placebo
see intervention
干预措施: Placebo (Drug)
Gardasil 9
see intervention
干预措施: Gardasil 9 Suspension for Injection (Drug)
结局指标
主要结局
Does additional HPV vaccination reduce the recurrence of vHSIL compared to placebo?
时间窗: 24 months after last inclusion
Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months
次要结局
- 8. Is Quality of life (measured with Euroqol 5D-5L questionnaire) improved after vaccination compared to placebo?(24 months after last inclusion)
- 8. Is sexual health (measured with Female Sexual Function Index, FSFI questionnaire) improved after vaccination compared to placebo?(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)
- 6. What is the level of antibodies at baseline and after (placebo) vaccination?(24 months after last inclusion)
- 7. Is the intervention cost effective?(24 months after last inclusion)
- 9. What is the effect of vaccination versus placebo on CIN/cervical cytology of the uterine cervix?(24 months after last inclusion)
- 10. Long-term follow-up: Is there a difference between vaccination and placebo group in number of recurrences of vHSIL (5 and 10 years) and the occurrence of vulvar malignancies (2, 5 and 10 years)?(5 and 10 year)
- 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)
研究者
Ralf van de Laar
MD, gynaecologic oncologist.
Erasmus Medical Center