The objective of this trial is to assess the immunological activity of Vvax001 by monitoring HPV-16 specific immune responses in order to determine the optimal dose inducing the highest immune responses.
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is the immunogenicity of Vvax001. By monitoring HPV-16
E6,7-specific T-cell immune responses, the optimal dose inducing the highest
immune responses will be determined.
Secondary outcome
The secondary parameters are side effects/ adverse events related to Vvax001.
Toxicity will be graded according to the NCI Common Terminology Criteria for
Adverse Events (CTCAE) Version 4.0.
The injection sites will be screened for local transformation by means of
inspection and palpation. If indicated, imaging (e.g. ultrasound) and/or biopsy
will be performed. Screening of the injection sites will be performed during
visit 3, 5 and 6.
Background summary
HPV infection is an important cause of premalignant genital and oropharyngeal
lesions, cervical cancer, vulvar cancer, anal cancer, and penile cancer.
HPV-induced cancer is the second largest cause of cancer deaths in women
worldwide. Current treatment for premalignant HPV-induced genital lesions
primarily relies on surgery, which is highly discomforting and carries a risk
of complications like bleeding, stenosis and/or cervical incompetence which may
lead to infertility. Above all, it does not eradicate the underlying HPV
infection.
Therapeutic immunization is an attractive alternative to the current options
for treating precancerous lesions and (invasive) cancer. The immune cells
induced by cancer immunotherapy can target the tumor cells and kill them. When
long-lasting immunity is induced the immunotherapy may prevent recurrence of
the disease. Hence, the approach taken in this study, is to immunize with a
replication-incompetent Semliki Forest Virus (SFV) vector encoding HPV-related
tumor antigens. Intramuscular immunization with these replication-incompetent
SFV particles (Vvax001) is aimed at eliciting a therapeutic anti-tumor
response.
Study objective
The objective of this trial is to assess the immunological activity of Vvax001
by monitoring HPV-16 specific immune responses in order to determine the
optimal dose inducing the highest immune responses.
Study design
In this phase I immunization study, four dose levels of Vvax001 will be tested;
5x10^5, 5x10^6, 5x10^7 and 2,5x10^8 Infectious Particles (IP) Vvax001. Patients
will receive three consecutive doses, with an interval of 3 weeks. Each dose is
administered intramuscularly bilaterally and consists of two injections of 1 ml
each (total 2 ml). Cohorts of 3 patients will be treated per dose level.
Although no limiting toxicities are anticipated based on previous experience
with similar viral vector vaccines, enrollment of subsequent patients will
proceed with an interval of 48 hours.
Participants will be observed for 4 hours at the treatment site ( 1hr after 2nd
and 3rd vaccination) and will be contacted by telephone 6-8 hours after
immunization in order to obviate any adverse events (AEs).
Intervention
Patients will receive three intramuscular immunizations with a 3-week interval.
Patient evaluation will be performed before, immunization including history,
physical examination, full blood count, urea, electrolytes and liver function
tests and a pregnancy test. Participants will be observed for 4 hours at the
treatment site (1hr after 2nd and 3rd vaccination) and will be contacted by
telephone 6-8 hours after immunization in order to obviate any adverse events
(AEs).
Peripheral blood mononuclear cells (PBMC) will be collected at baseline, 7-10
days after the second immunization, and 7-10 days after the third immunization
to monitor HPV-specific immune responses.
Study burden and risks
The burden in this phase I trial is relatively low. The study procedures
require 6 visits to the hospital. Immunization by intramuscular injection is
performed three times. Six venepunctions will be performed for PBMC collection
and biochemistry.
Toxicity will be graded according to the NCI Common Terminology Criteria for
Adverse Events (CTCAE) Version 4.0. Given the design of the Vvax001 vaccine,
the results of preclinical animal studies, and previous clinical experience
with similar viral vector vaccines, little toxicity is anticipated from
intramuscular administration of Vvax001.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
Patients with a history of cervical intraepithelial neoplasia (CIN) II and III and patients with a history of cervical cancer, both minimally 12 weeks after completion of treatment.
Exclusion criteria
- Prior treatment with immunotherapeutic agents against HPV
- History of an autoimmune disease or other systemic intercurrent disease that might affect the immunocompetence of the patient, or current or prior use ( 4 weeks before start of the study) of high dose immunosuppressive therapy.
- History of a second malignancy except curatively treated low-stage tumors with a histology that can be differentiated from the cervical cancer type
- Participation in a study with another investigational drug within 30 days prior to the enrolment in this study
- Any condition that in the opinion of the investigator could interfere with the conduct of the study
- Pregnancy
Design
Recruitment
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 | EUCTR2015-004979-74-NL |
| CCMO | NL56680.000.16 |