Adjuvant Nonavalent HPV Vaccination in Women Treated for Vulvar HSIL
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexFemale
Age18-100
SponsorErasmus Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Women 18 years or older
Vulvar High-grade Squamous Intraepithelial Lesion (vHSIL), histologically proven
Planned for treatment (surgical, laser or imiquimod) for vHSIL
Disqualifiers
Prior HPV vaccination
(Micro-) invasive carcinoma or history of HPV related genital carcinoma (cervix, anal, vulva)
Pregnancy
Women allergic to vaccine components
Trial design
Design model
Parallel
Treatments tested in this trial
Gardasil 9 Suspension for Injection
DrugAfter 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
DrugAfter 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.
Treatment groups
500 Participants
are divided into 2 treatment groupsGroup A: Gardasil 9Experimental treatment 1 intervention
Group B: placeboPlacebo comparator 1 intervention
Trial outcomes
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
Time frame
24 months after last inclusionSecondary outcomes
1
1. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months?
1\. Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months
Time frame
6 and 12 months after last inclusion2
2. What is the effectiveness (complete remission) after treatment in vaccination versus placebo at 6 and 12 months in primary episode vHSIL versus recurrence?
2\. Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between HPV vaccination and placebo at 6 and 12 months for primary vHSIL versus recurrent vHSIL.
Time frame
6 and 12 months after last inclusion3
3. What is the effectiveness of adjuvant vaccination in different treatments of vHSIL (laser, imiquimod, excision) at 24 months?
3\. Difference in number and percentage of patients with clinical recurrence rate of vulvar HSIL between the different treatment modalities
Time frame
24 months after last inclusion4
4. How often is additional treatment for vHSIL needed in the study period? Is this different between the study groups?
4\. Difference in number and percentage for additional treatment necessary after primary treatment.
Time frame
24 months after last inclusionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Erasmus Medical Center
Lead sponsor
Dutch Cancer Society
Collaborator
Source ClinicalTrials.gov