The primary objective of the current study is to assess the efficacy of qHPV vaccination in preventing recurrence of high-grade AIN in HIV+ MSM with CD4 counts >350 x 10E6/l who were successfully treated for high-grade intra-anal AIN in the past…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Gastrointestinal neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Screening for AIN will be performed by high-resolution anoscopy (HRA), at
inclusion (first vaccination) and at last vaccination (6 months), and repeated
at 6 and 12 months after the last vaccination. Safety Monitoring for
spontaneous adverse events and injection-site reactions will be performed one
week after each vaccination and thereafter every 6 months for a total of 12
months of follow-up.
Primary end point will be the cumulative recurrence of HG AIN at 12 months
after the last vaccination, as assessed by HRA (High-Resolution Anoscopy), with
biopsies taken of suspect lesions.
Secondary outcome
Secondary outcome measures are toxicity/ safety, recurrence of HG AIN at last
vaccination and 6 months afterwards, cumulative occurrence of LG AIN at 12
months after the last vaccination, cumulative occurrence of anogenital warts at
12 months after the last vaccination, causative HPV type in recurrent AIN
lesions, as assessed by LCM (Laser Capture Microdissection)/ PCR (polymerase
chain reaction), and HPV type-specific antibody response.
Background summary
Since the introduction of combination antiretroviral therapy (cART), human
immunodeficiency virus (HIV)-related morbidity and mortality have considerably
decreased. However, as a result of the significantly prolonged life span, new
causes of morbidity and mortality have become evident. In particular, anal
cancer incidence has increased dramatically in HIV-positive men. Like cervical
cancer, anal cancer is causally linked to infections with high-risk
papillomaviruses, and is preceded by precursor lesions: anal intraepithelial
neoplasia (AIN). Over 90% of HIV-positive MSM (men who have sex with men) have
persisting anal HPV (human papilloma virus) infection, and high-grade (HG) AIN
is present in 30% of all HIV+ MSM.
As in cervical intraepithelial neoplasia, early diagnosis and treatment of AIN
have been advocated to prevent malignancy. Electrocoagulation/ cauterization is
standard of care for intra-anal AIN, but after treatment, recurrence of lesions
occurs in approx. 50% of cases. This is a major problem in an effective
screening program for AIN.
In a nonconcurrent, nonblinded cohort study qHPV (quadrivalent human papilloma
virus) vaccination significantly (HR 0.50) reduced HG AIN recurrence among MSM
successfully treated for AIN. This is in accordance with findings in women
treated for cervical intraepithelial neoplasia. Previous vaccination with
quadrivalent HPV vaccine among women who had surgical treatment for HPV related
disease significantly reduced the incidence of subsequent HPV related disease,
including high grade disease.
Therefore, a strategy that is worth investigating is vaccination with the qHPV
vaccine to prevent recurrences in HIV+ MSM who were successfully treated for HG
AIN.
Study objective
The primary objective of the current study is to assess the efficacy of qHPV
vaccination in preventing recurrence of high-grade AIN in HIV+ MSM with CD4
counts >350 x 10E6/l who were successfully treated for high-grade intra-anal
AIN in the past year.
Study design
A multicentre, randomised, double-blind clinical trial in three hospitals in
the Netherlands.
Patients are randomised for vaccination with the quadrivalent HPV vaccine
(Gardasil ®) or vaccination with a matching placebo at months 0, 2 and 6.
Intervention
Patients are randomised for vaccination with the quadrivalent HPV vaccine
(Gardasil ®) or vaccination with a matching placebo at months 0, 2 and 6.
Randomisation will be stratified for complete response versus partial response
(from HG AIN to low-grade (LG) AIN) of the initial HG AIN lesion, and for
treatment less than 6 months ago versus treatment more than 6 months ago.
Study burden and risks
HIV+ MSM who were successfully treated for HG AIN are still at a 50% risk for
recurrences, with additional treatment sessions needed, and an ongoing risk for
malignant degeneration of lesions.
Costs of 3 vaccinations are approx. ¤ 400, but if vaccination reduces
recurrence rates by 50%, this will be a highly cost-effective intervention,
very likely to be introduced into regular care.
For the study, patients will be vaccinated 3 times with the quadrivalent
vaccine Gardasil ® or placebo, and will undergo two extra HRA*s. Clinical trial
data show that the most common adverse events of Gardasil ® were mild or
moderate, so few risks are associated with study participation.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
• Written informed consent
• HIV+ males having sex with males (MSM), CD4 count > 350/ul.
• Biopsy-proven intra-anal high-grade AIN successfully treated in the past year with cauterization, cryotherapy, Efudix, imiquimod or another form of local treatment. Lesions with regression from HG to Low grade (LG) AIN will also be eligible.
• Lesion (still) in remission at the moment of first vaccination (a maximum interval of 6 weeks between last HRA and first vaccination is allowed).
• Good performance status (a Karnofsky performance score of >= 60 [on a scale of 0 to 100, with higher scores indicating better performance status])
• Normal pretreatment laboratory blood values
Exclusion criteria
• Immunosuppressive medication or other diseases associated with immunodeficiency
• Life expectancy less than one year
• Previous vaccination with the bivalent or quadrivalent HPV vaccine
• History of anal carcinoma
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002009-70-NL |
| CCMO | NL45200.018.13 |