To study the safety, toxicity and immunogenicity of a naked DNA vaccine encoding the shuffled HPV16 E7 gene product (TTFC-E7SH) in patients with HPV16+ VINIII lesions.
ID
Source
Brief title
Condition
- Reproductive neoplasms female benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• To study the safety and toxicity of two different doses of the naked DNA
vaccine encoding the shuffled HPV16 E7 gene products (TTFC-E7SH).
• To study the HPV-specific immune response in two different doses of
TTFC-E7SH.
Secondary outcome
• To study the clinical response to vaccination of two different doses of
TTFC-E7SH
Exploratory objectives:
• Local immune response
HPV16-specific proliferative capacity will be tested in triplicate in a 3 day
proliferation assay.
• Tumour microenvironment
The effect of vaccination on the tumour microenvironment will be determined by
multicolour fluorescent immunohistochemistry.
Background summary
Human papilloma virus (HPV) infection is strongly associated with the
development of squamous cell cancer in the anogenital and head and neck region.
HPV16 infection may also cause a chronic skin disorder of the vulva known as
vulvar intraepithelial neoplasia (VIN). Patients often have a weak or no
spontaneous HPV-specific T cell response which is thought to be important in
the clearance of infection and disease. VIN is a chronic disease with high
relapse rates after standard treatments. Spontaneous regression are found in
1.2% op patients. Because the persistence of oncogenic HPV proteins E6 and E7
is required for carcinogenesis, these viral antigens are exquisite targets for
immunotherapeutic interventions.
Here we propose to initiate a phase I study in patients with HPV16-positive
VINIII lesion using a novel and potent intradermal HPV DNA vaccination
strategy. In preclinical studies this strategy was shown to be much more potent
in the induction of (E6 and) E7-specific CD8+ cytotoxic T-cell immunitiy than
existing DNA vaccination strategies, providing a strong rationale for its
clinical evaluation. In this phase I study we will define the safety, toxicity
and immunogenicity of this highly promising DNA vaccination strategy in
patients with a HPV-positive VINIII lesion. This study will allow us to define
the optimal dosage and value of this novel DNA vaccination strategy for the
treatment of HPV-associated (pre)malignancies.
Study objective
To study the safety, toxicity and immunogenicity of a naked DNA vaccine
encoding the shuffled HPV16 E7 gene product (TTFC-E7SH) in patients with HPV16+
VINIII lesions.
Study design
Phase I immunogenicity/toxicity-evaluation in 12 patients.
Intervention
TTFC-E7SH will be injected intradermally on days 0, 3 and 6 using a permanent
make-up device, and boost vaccinations will be given after 4 weeks (day 28, 31
and 34).
Study burden and risks
Patients will be vaccinated 6 times with TTFC-E7SH using a permanent make-up
device. Further, they will undergo 5 bloodtest, 3 urinetest, 3 times a skin
biopsy and twice a biospy of the VIN lesion. They will come 11 times to the
outpatients clinic for the before mentioned tests and physical examinations.
See protocol for the complete schedule.
The vaccine that is being used in this clinical trial does not contain factors
favoring integration, nor does it contain sequences that can lead to
replication, or that can become part of viruses or bacteria. Preclinical data
show that intradermal DNA vaccination is much more potent than classical
intramuscular injection. Tattooin of skin is a commonly used method for
treatment of scars or as part of reconstructive surgery. Tattooing may induce a
burning sensation during tattooing, which will stop the moment the tattooing is
ended. Furtermore, flulike symptoms with fever during 48 hours after
vaccination can occur.
This investigation can lead to a more effective therapy for patients with
HPV-associated (pre)malignincies. There are no persistent or severe side
effects known for this treatment. Therefor we consider the physical discomfort
associated with participation in this study as acceptable.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
* Age above 18 years
* Willing and able to undergo the planned study procedures
* Written informed consent
* Histologically proven visible VINIII lesion (last histology <=3 months prior to enrolment)
* HPV16+ VINIII lesion (to be determined on archival tumour tissue (<=10 years old); if that is not available a biopsy will be required)
* No indication of an active infectious disease
* No history of autoimmune disease or systemic undercurrent disease which might affect immunocompetence
* Adequate bonemarrow, renal function and liver function
Exclusion criteria
* Prior treatment with anti-HPV agents
* Participation in a study with another investigational drug within 30 days prior to the enrolment in this study
* Severe cardiac, respiratory or metabolic disease
* Use of steroids or other immunosuppressive drugs
* Use of oral anticoagulant drugs
* History of a malignancy except curatively treated low-stage tumour
* Severe infections requiring antibiotic
* Any treatment for the VINIII lesion within 6 weeks prior to enrolment
* Lactation or pregnancy (if applicable)
* Not willing to take adequate contraceptive measures (if applicable)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000610-38-NL |
| CCMO | NL46637.000.13 |
| OMON | NL-OMON27857 |