Therapeutic HPV-16 Vaccination for the Treatment of Anal Dysplasia (VACCAIN-T)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
Prof. Jan Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01923116
First received: August 6, 2013
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

Rationale:

Anal cancer incidence has increased dramatically in HIV (human immunodeficiency virus)-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). Several treatment options exist for AIN, but success rates are disappointingly low. An alternative strategy might be therapeutic HPV (human papilloma virus) vaccination. In women with vulvar intraepithelial neoplasia (VIN), a condition with a comparable pathogenesis, therapeutic vaccination with HPV-16 viral oncoproteins E6 and E7, was well tolerated, and proved to be effective.

Objective:

The objective of the current proposal is to assess, in a phase 1/2 study, the safety and efficacy of this synthetic vaccine SLP-HPV-01® in HIV+ men with CD4 counts > 350 x 10E6/l and intra-anal high-grade, HPV16 positive AIN, who failed on previous treatment.

Study population:

HIV-positive MSM (men who have sex with men) with a CD4 count > 350 cells/ul with HPV16-induced intra-anal high-grade AIN (grade 2-3) that was resistant to, or recurred after conventional cauterization or other forms of local treatment.

Study design:

The first phase of the study is a dose-response study, with 3 different dosage schedules (1,5,10; 5,10,20; and 10,20,40 μg of SLP-HPV-01®, administered intradermally with a three-week interval), each dosage schedule with or without the co-administration of pegylated interferon-α (Pegintron 1 μg/kg s.c.) at the day of vaccine administration. Each vaccination schedule is to be tested in 5 patients.

The vaccination schedule that induces in HIV-positive MSM the best HPV16-specific response compared to that of the women with VIN in our previous study, is considered the optimal schedule. The size of this dose group will be increased to a total of 20 patients by treating an additional 15 patients.

Intervention:

Patients will be vaccinated 3 times with a 3-week interval with the SLP-HPV-01® vaccine.

Endpoints:

The primary clinical end points will be both toxicity/ safety, and the regression of the lesions at 3, 6 and 12 months, as assessed by HRA (high resolutions anoscopy), with biopsies taken of lesion sites.

Secondary endpoints are regression of lesions at 18 months and HPV16-specific immunity in blood will be measured: i.e. ELISPOT (IFNg) for ex-vivo detection of antigen-specific responses and multiparametric intracellular cytokine/extracellular activation marker staining to determine the type (CD4+ and/or CD8+) and function (activation status and/or cytokines) of T-cells that respond.


Condition Intervention Phase
Anal Intraepithelial Neoplasia
HIV
Drug: HPV-16 vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Therapeutic Vaccination Against Human Papillomavirus Type 16 for the Treatment of Anal Intraepithelial Neoplasia in HIV+ Men

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Safety of the HPV-16 vaccine in HIV+ MSM [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]
    Monitoring for spontaneous adverse events and injection-site reactions will be done weekly for three weeks after each vaccination. Clinical assessments and laboratory tests (routine hematology and chemistry) will be performed before the second and third vaccination and thereafter every 3 months for a total of 18 months of follow-up. Adverse events are graded according to version 3.0 of the Common Terminology Criteria for Adverse Events (CTCAE), which grades events on a scale of 1 to 5, with higher grades indicating greater severity.


Secondary Outcome Measures:
  • Regression of the AIN lesion [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    High resolution anoscopy is performed to monitor the AIN lesions. Biopsies will be obtained of suspected lesions. Complete response is defined as histological resolution of AIN, partial response is defined as regression from high grade to low grade AIN. In case of persisting high grade AIN, a partial response is defined as a decrease in lesion size of 50% or more.


Other Outcome Measures:
  • HPV16-specific immunity in blood [ Time Frame: 3 weeks after last vaccination ] [ Designated as safety issue: No ]

    In order to assess the systemic changes in immunity, which are induced by vaccination we will examine venous blood samples by using peripheral blood lymphocytes that are tested by a set of complementary T-cell assays: i.e. proliferation (LST), cytokine production (IFNg, TNFa, IL-4, IL-5, IL-10, and IL-2) as well as by ELISPOT (IFNg) for ex-vivo detection of antigen-specific responses and by multiparametric intracellular cytokine/extracellular activation marker staining to determine the type (CD4+ and/or CD8+) and function of T-cells that respond.

    A vaccine-induced response is defined as a 3-fold increase compared to the pre-vaccination result.



Estimated Enrollment: 45
Study Start Date: August 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HPV-16 vaccine Drug: HPV-16 vaccine
Vaccination with SLP-HPV-01® with or without interferon-a injections.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • HIV+, CD4 count > 350/ul
  • Biopsy-proven intra-anal high-grade AIN caused by HPV16, resistant to, or recurring after previous treatment with cauterization (or other local treatment), 5-fluorouracil or imiquimod.
  • Good performance status (a Karnofsky performance score of ≥60.
  • Normal pretreatment laboratory blood values as described previously.

Exclusion Criteria:

  • Immunosuppressive medication or other diseases associated with immunodeficiency
  • Life expectancy < 1 year
  • History of anal carcinoma
  • IFN-α criteria (see SmPC): severe cardiac, thyroid, hepatic or central nervous system disease, including severe depression in the past.
  • Current hepatitis C treatment with IFN-α
  • Previous vaccination against HPV
  Contacts and Locations
Choosing 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: NCT01923116

Contacts
Contact: Karien CM Gosens, MD 0031205662575 k.c.gosens@amc.nl
Contact: Jan M Prins, prof, MD 0031205664380 j.m.prins@amc.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Contact: Karien CM Gosens, MD    0031205662575    k.c.gosens@amc.nl   
Principal Investigator: Jan M Prins, prof, MD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Jan M Prins, professor Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided

Responsible Party: Prof. Jan Prins, Prof. dr. J.M. Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01923116     History of Changes
Other Study ID Numbers: NL42802.000.12
Study First Received: August 6, 2013
Last Updated: March 7, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Anal intraepithelial neoplasia
HIV
HPV
Vaccination
Treatment

Additional relevant MeSH terms:
Neoplasms
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 29, 2014