CIN3Phase 2VvaxNCT06015854
Vvax001 Cancer Vaccine in Premalignant Cervical Lesions - Phase II
A Phase 2 study testing Vvax001 therapeutic cancer vaccine in people with CIN3 and Cervical Intraepithelial Neoplasia, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
This is an open label phase II study in patients with newly diagnosed human papilloma virus type 16 (HPV16) induced cervical intraepithelial neoplasia grade 3 (CIN3). Patients will be treated with three doses of Vvax001 immunization with an interval of 3 weeks between each immunization to induce histopathological… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- CIN3, Cervical Intraepithelial Neoplasia, Cervical Intraepithelial Neoplasia Grade 3
- What is being tested?
- Vvax001 therapeutic cancer vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Mar 2021to 1 Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed HPV16-positive CIN3.
- Age of 18 years and older.
- Patients of child-bearing potential should test negative using a serum pregnancy test and agree to utilize effective contraception during the entire treatment and follow-up period of the study.
- Written informed consent according to local guidelines.
Who cannot join
- PAP5 lesions.
- Previously undergone treatment for CIN lesions.
- Adenocarcinoma in situ within CIN3 lesion.
- 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 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.
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- Clinically significant findings as judged by the Investigator on screening/study entry including those from the Biochemistry, Hematology and urinalysis performed at baseline.
- Any condition that in the opinion of the investigator could interfere with the conduct of the study.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Groningen (UMCG)
Groningen, 9700 RB
Anneke Eerkens, MSc, 0015 361 6161, a.l.eerkens@umcg.nl
Refika Yigit, MD, PhD
About this study
Official title: A Phase II Study to Determine the Efficacy and Safety of Vvax001, a Therapeutic Semliki Forest Virus Based Cancer Vaccine, in Patients With HPV-16 Induced Grade 3 Cervical Intraepithelial Neoplasia
This is an open label phase II study in patients with newly diagnosed human papilloma virus type 16 (HPV16) induced cervical intraepithelial neoplasia grade 3 (CIN3). Patients will be treated with three doses of Vvax001 immunization with an interval of 3 weeks between each immunization to induce histopathological regression and HPV clearance. Regression of CIN3 lesions will be monitored using colposcopy in week 9, week 17 and week 25. When complete regression of the CIN3 lesion is observed by colposcopy, a biopsy will be taken in week 25 to confirm regression histologically. A positive histologic regression is defined as a reduction from CIN3 to CIN1 or no dysplasia. Patients with a complete regression will not undergo the standard-of-care loop excision of the transformation zone (LETZ) and will be followed-up after the study by cytology at 3, 6 and 12 months. If complete regression has not occurred by 25 weeks, a standard-of-care LETZ will be performed.
Read the detailed description
Human papillomavirus (HPV) infection is the most important cause of premalignant cervical disease. Current treatment for premalignant HPV-induced genital lesions primarily relies on surgery, which can be discomforting and carries a risk of complications like bleeding, cervical stenosis and/or incompetence which may lead to infertility and partus prematuris/immaturis. Above all, it does not necessarily eradicate the underlying HPV infection completely.
Therapeutic immunization is a very attractive alternative to the current treatment options for 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. Therefore, the approach taken in this study is to immunize with a replication-incompetent Semliki Forest Virus (SFV) vector encoding HPV-derived tumor antigens. Intramuscular immunization with these replication-incompetent SFV particles (Vvax001) is aimed at eliciting a therapeutic anti-tumor response.
A phase I study has been conducted in which vaccination with Vvax001 induced HPV16-E6,7-specific immune responses in women previously treated for cervical intraepithelial neoplasia (CIN) or cervical cancer (CC). Intramuscular immunization with Vvax001 was well tolerated, showing only mild to moderate local adverse reactions. Altogether, the data of this study justify testing of Vvax001 in CIN3 patients in the current phase II study.
In this open label phase II study patients with newly diagnosed HPV16 induced cervical intraepithelial neoplasia grade 3 (CIN3) will receive three bilateral intramuscular immunizations of Vvax001 (5x107 infectious particles [IP]) with an interval of 3 weeks between vaccinations at week 0, week 3 and week 6.
Patients will be monitored for regression of CIN3 lesions by colposcopy and digital imaging at week 9, week 17 and week 25. When complete regression of the CIN3 lesion is observed by colposcopy, a biopsy will be taken in week 25 to confirm regression and no LETZ will be performed. If complete regression has not occurred by 25 weeks, the standard-of-care LETZ will be performed. If progression of the CIN3 lesion is observed during the 25 week interval, a biopsy will be taken to confirm pathological progression. If pathological progression has occurred, patients will immediately undergo a LETZ. If no pathological progression has occurred, patients will continue to be monitored by colposcopy.
Patients with a complete regression will be followed-up by cytology at 3, 6 and 12 months after exit from the study. Hereafter, patients will be monitored through regular screening programs.
- Conditions
- CIN3, Cervical Intraepithelial Neoplasia, Cervical Intraepithelial Neoplasia Grade 3, HPV 16 Infection
- Being tested
- Vvax001 therapeutic cancer vaccine
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vvax001 therapeutic cancer vaccineBiological
Patients will receive three immunizations, with an interval of 3 weeks between each immunization at weeks 0, 3 and 6. Each vaccination will be given as two injections; 1 injection in each leg. The injections will be administered intramuscularly in the upper legs, preferably in the m. vastus lateralis.
| Study group | Role | What they receive |
|---|---|---|
| HPV16+ CIN3 | Experimental | Patients with histological proven HPV16-positive cervical intraepithelial neoplasia grade 3. Receives: Biological: Vvax001 therapeutic cancer vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical efficacy of Vvax001
Clinical efficacy is determined by a pathological regression of the premalignant CIN3 lesion in pre- versus post-treatment tissue samples. A positive histologic regression is defined as a reduction from CIN3 to CIN1, or a reduction from CIN3 to no dysplasia.
Measured: At week 25 (19 weeks after the last immunization)
Secondary outcomes (3)
Immunogenicity of Vvax001
HPV-16 E6,7-specific T-cell immune responses in the peripheral blood will be measured by IFN-y ELISPOT
Measured: At weeks 7, 9, 17 and 25, respectively 1 week, 3 weeks, 11 weeks and 19 weeks after the last vaccination
HPV 16 clearance
Standard HPV testing by molecular analysis will be performed on tissue collected during the last study visit.
Measured: Week 25 (19 weeks after the last immunization)
Side effects/ adverse events
To monitor the side effects/ adverse events related to intramuscular administration of Vvax001. Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Measured: up to 19 weeks after the last immunization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study start23 Mar 2021
- Primary completion6 Feb 2024 (estimated)
- Study completion1 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CIN3Studies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society, ViciniVax B.V
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06015854
- Sponsor's protocol ID
- Vvax001-UMCG-02
- Acronym
- Vvax
- Status last verified
- Aug 2023
- First submitted
- 23 Aug 2023
- Last updated
- 29 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Determine the Efficacy and Safety of Vvax001, a Therapeutic Semliki Forest Virus Based Cancer Vaccine, in Patients With HPV-16 Induced Grade 3 Cervical Intraepithelial Neoplasia
- ClinicalTrials.gov ID
- NCT06015854
- Acronym / sponsor ID
- Vvax / Vvax001-UMCG-02
- Conditions
- CIN3, Cervical Intraepithelial Neoplasia, Cervical Intraepithelial Neoplasia Grade 3, HPV 16 Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Dutch Cancer Society, ViciniVax B.V
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 6 Feb 2024 (estimated)
- Study completion
- 1 Apr 2024 (estimated)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label phase II study in patients with newly diagnosed human papilloma virus type 16 (HPV16) induced cervical intraepithelial neoplasia grade 3 (CIN3). Patients will be treated with three doses of Vvax001 immunization with an interval of 3 weeks between each immunization to induce histopathological regression and HPV clearance. Regression of CIN3 lesions will be monitored using colposcopy in week 9, week 17 and week 25. When complete regression of the CIN3 lesion is observed by colposcopy, a biopsy will be taken in week 25 to confirm regression histologically. A positive histologic regression is defined as a reduction from CIN3 to CIN1 or no dysplasia. Patients with a complete regression will not undergo the standard-of-care loop excision of the transformation zone (LETZ) and will be followed-up after the study by cytology at 3, 6 and 12 months. If complete regression has not occurred by 25 weeks, a standard-of-care LETZ will be performed.
Detailed description
Human papillomavirus (HPV) infection is the most important cause of premalignant cervical disease. Current treatment for premalignant HPV-induced genital lesions primarily relies on surgery, which can be discomforting and carries a risk of complications like bleeding, cervical stenosis and/or incompetence which may lead to infertility and partus prematuris/immaturis. Above all, it does not necessarily eradicate the underlying HPV infection completely.
Therapeutic immunization is a very attractive alternative to the current treatment options for 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. Therefore, the approach taken in this study is to immunize with a replication-incompetent Semliki Forest Virus (SFV) vector encoding HPV-derived tumor antigens. Intramuscular immunization with these replication-incompetent SFV particles (Vvax001) is aimed at eliciting a therapeutic anti-tumor response.
A phase I study has been conducted in which vaccination with Vvax001 induced HPV16-E6,7-specific immune responses in women previously treated for cervical intraepithelial neoplasia (CIN) or cervical cancer (CC). Intramuscular immunization with Vvax001 was well tolerated, showing only mild to moderate local adverse reactions. Altogether, the data of this study justify testing of Vvax001 in CIN3 patients in the current phase II study.
In this open label phase II study patients with newly diagnosed HPV16 induced cervical intraepithelial neoplasia grade 3 (CIN3) will receive three bilateral intramuscular immunizations of Vvax001 (5x107 infectious particles [IP]) with an interval of 3 weeks between vaccinations at week 0, week 3 and week 6.
Patients will be monitored for regression of CIN3 lesions by colposcopy and digital imaging at week 9, week 17 and week 25. When complete regression of the CIN3 lesion is observed by colposcopy, a biopsy will be taken in week 25 to confirm regression and no LETZ will be performed. If complete regression has not occurred by 25 weeks, the standard-of-care LETZ will be performed. If progression of the CIN3 lesion is observed during the 25 week interval, a biopsy will be taken to confirm pathological progression. If pathological progression has occurred, patients will immediately undergo a LETZ. If no pathological progression has occurred, patients will continue to be monitored by colposcopy.
Patients with a complete regression will be followed-up by cytology at 3, 6 and 12 months after exit from the study. Hereafter, patients will be monitored through regular screening programs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HPV16+ CIN3 | Experimental | Biological: Vvax001 therapeutic cancer vaccinePatients with histological proven HPV16-positive cervical intraepithelial neoplasia grade 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Newly diagnosed HPV16-positive CIN3.
- Age of 18 years and older.
- Patients of child-bearing potential should test negative using a serum pregnancy test and agree to utilize effective contraception during the entire treatment and follow-up period of the study.
- Written informed consent according to local guidelines.
Key exclusion criteria (9 listed)
- PAP5 lesions.
- Previously undergone treatment for CIN lesions.
- Adenocarcinoma in situ within CIN3 lesion.
- 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 malignancy except curatively treated low-stage tumors with a histology that can be differentiated from the cervical cancer type.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vvax001 therapeutic cancer vaccinePatients will receive three immunizations, with an interval of 3 weeks between each immunization at weeks 0, 3 and 6. Each vaccination will be given as two injections; 1 injection in each leg. The injections will be administered intramuscularly in the upper legs, preferably in the m. vastus lateralis. | Biological | HPV16+ CIN3 |
Primary outcome
Clinical efficacy of Vvax001
Time frame: At week 25 (19 weeks after the last immunization)
Clinical efficacy is determined by a pathological regression of the premalignant CIN3 lesion in pre- versus post-treatment tissue samples. A positive histologic regression is defined as a reduction from CIN3 to CIN1, or a reduction from CIN3 to no dysplasia.
3 secondary outcomes
Immunogenicity of Vvax001
Time frame: At weeks 7, 9, 17 and 25, respectively 1 week, 3 weeks, 11 weeks and 19 weeks after the last vaccination
HPV 16 clearance
Time frame: Week 25 (19 weeks after the last immunization)
Side effects/ adverse events
Time frame: up to 19 weeks after the last immunization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Individual participant dataSharing planned: Undecided
Related trials for CIN3
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Urine HPV Testing for Cervical Cancer Screening Among Women Living With HIV in South Africa
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Adjuvant 5-Fluorouracil Following Thermal Ablation to Improve HPV Treatment Outcomes in Women With HIV in Kenya
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I) Atypical Squamous Cells of Undetermined Significance (ASC-US), II) Atypical Glandular Cells of Uncertain Significance (AGUS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vvax001 therapeutic cancer vaccine in people with CIN3 and Cervical Intraepithelial Neoplasia, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yigit (003153616161, r.yigit@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical efficacy of Vvax001 (time frame: At week 25 (19 weeks after the last immunization)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.