HPV (Human Papilloma Virus) Vaccination After Treatment of Anal Intraepithelial Neoplasia (AIN) (VACCAIN-P)
Verified August 2016 by Prof. Jan Prins
Prof. Jan Prins
Information provided by (Responsible Party)
Prof. Jan Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First received: March 7, 2014
Last updated: August 5, 2016
Last Verified: August 2016
History of Changes
This study evaluates vaccination with the quadrivalent HPV vaccine (Gardasil) versus placebo vaccination on prevention of high grade AIN recurrence in HIV-positive MSM (men who have sex with men) who were successfully treated for high grade AIN.
Biological : Gardasil
Drug : Placebo
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Quadrivalent HPV Vaccination After Effective Treatment of Anal Intraepithelial Neoplasia in HIV+ Men|
Further study details as provided by Prof. Jan Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Primary Outcome Measures
- Cumulative recurrence of intra-anal or peri-anal HG AIN at 12 months after the last vaccination (18 months after inclusion), as assessed by HRA, with biopsies taken of suspect lesions. [ Time Frame: 18 months ]
- Toxicity/ safety of the Gardasil vaccine in HIV+ MSM.
[ Time Frame: 18 months ]
One week after each vaccination and during all follow up visits the most common adverse events of Gardasil and other eventually occuring complaints will be evaluated by history taking. Adverse events will be graded according to the CTCAE v4 (Common Terminology Criteria for Adverse Events), which grades events on a scale of 1 to 5, with higher grades indicating greater severity.
- Recurrence of intra-anal or peri-anal HG AIN at the moment of last vaccination and 6 months afterwards. [ Time Frame: 6 and 12 months ]
- Cumulative occurrence of intra-anal or peri-anal LG AIN at 12 months after the last vaccination.
[ Time Frame: 18 months ]
The patients with LG AIN at inclusion are excluded from this analysis.
- Cumulative occurrence of anogenital warts at 12 months after the last vaccination.
[ Time Frame: 18 months ]
Evaluated by physical examination and history taking.
- Causative HPV type in recurrent AIN lesions, as assessed by LCM/ PCR. [ Time Frame: 18 months ]
- HPV type-specific antibody response. [ Time Frame: 9 months (3 months after last vaccination) ]
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||September 2018|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Intramuscular Gardasil vaccination at 0, 2 and 6 months.
Intramuscular Saline 0.9% vaccination at 0, 2 and 6 months
injection of 0.9% saline
Other Name: intramuscular Saline 0.9%
Rationale: 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, non-blinded 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.
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 population: HIV-positive MSM with a CD4 count > 350 cells/ul and intra-anal high-grade AIN (grade 2-3) that was successfully treated in the past year with conventional cauterization, cryotherapy, or other forms of local treatment.
Study design: A multicenter, randomised, double-blind clinical trial in four hospitals in the Netherlands.
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, for treatment less than 6 months ago versus treatment 6 months and longer ago, and for AMC versus other hospitals.
Main study parameters/endpoints: 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 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 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.
The total sample size is estimated to be 125 patients based on an expected recurrence rate of 50% within 12 months. Statistical analysis will be based on the intention-to-treat principle. Both primary and secondary endpoints will be analyzed by descriptive statistics and the chi-square test with a 0,05 two-sided significance level.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
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 HRAs. Clinical trial data show that the most common adverse events of Gardasil ® were mild or moderate, so few risks are associated with study participation.
|Ages Eligible for Study:||18 Years and older|
|Sexes Eligible for Study:||Male|
|Accepts Healthy Volunteers:||No|
- Written informed consent.
- Age ≥ 18 years.
- HIV+ MSM, CD4 count > 350/ul (maximum 6 months before screening visit).
- Biopsy-proven intra-anal high-grade AIN successfully treated in the past year with cauterization, cryotherapy, Efudix, imiquimod or another form of local treatment. A maximum interval of 1 year between last treatment and first vaccination is allowed. Lesions with regression from HG to LG AIN (AIN 1) will also be eligible.
- Lesions (still) in remission:
- Remission has to be established by 2 independent HRA anoscopists.
- A maximum interval of 3 months is allowed between the first of these HRAs and the first vaccination, and a maximum interval of 6 weeks is allowed between the second of these HRAs and the first vaccination.
- Biopsies of suspect lesions need to be obtained in one of the HRA sessions.
- Good performance status (a Karnofsky performance score of ≥ 60 [on a scale of 0 to 100, with higher scores indicating better performance status]).
- Pre-treatment haematology, and plasma ASAT, ALAT and creatinine levels compatible with study inclusion (maximum 6 weeks before screening visit).
- Immunosuppressive medication or other diseases associated with immunodeficiency.
- Life expectancy less than one year.
- Previous HPV vaccination.
- History of anal cancer.
- Other diseases not compatible with study participation.
- Allergy against constituent of Gardasil ® vaccine.
- Currently peri-anal AIN2 or 3.
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02087384
|Contact: Karien CM Gosens, MDfirstname.lastname@example.org|
|Contact: Jan M Prins, prof, MD, email@example.com|
Locations Show More
|DC Klinieken Oud Zuid||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1071 NX|
Contact: Arne van Eeden, MD  0031205730315  firstname.lastname@example.org
Principal Investigator: Arne van Eeden, MD
|Onze Lieve Vrouwe Gasthuis||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1090 HM|
Contact: Guido Berk van den, MD  0031205993503  email@example.com
Contact: Irina Cairo, MD  0031205992789  I.Cairo@olvg.nl
Principal Investigator: Guido van den Berk, MD
|Academic Medical Center||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1105 AZ|
Contact: Karien CM Gosens, MD  0031205662575  firstname.lastname@example.org
Sub-Investigator: Karien CM Gosens, MD
Principal Investigator: Jan M Prins, MD, prof
Sponsors and CollaboratorsProf. Jan Prins
|Principal Investigator:||Jan M Prins, prof, MD, infectiologist||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|Principal Investigator:||Henry JC de Vries, prof, MD, dermatologist||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|Responsible Party:||Prof. Jan Prins, Professor. dr. J.M. Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|ClinicalTrials.gov Identifier:||NCT02087384 History of Changes|
|Other Study ID Numbers:||NL45200.018.13|
|Study First Received:||March 7, 2014|
|Last Updated:||August 5, 2016|
Keywords provided by Prof. Jan Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):Anal intraepithelial neoplasia
Additional relevant MeSH terms:
Carcinoma in Situ
ClinicalTrials.gov processed this data on December 12, 2017
This information is provided by ClinicalTrials.gov.