This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies.
ID
Bron
Verkorte titel
Aandoening
DNA tattoo vaccination; uVIN; usual vulvar intraepithelial neoplasia; HPV16; sig-HELP-E6SH/E7SH-kdel; vulvaire intraepitheliale neoplasie; HPV vaccinatie
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Primary objectives:<br>
• To study the systemic HPV-specific immune response of two naked DNA vaccines
encoding sig-HELP-kdel and shuffled HPV16 E6 or E7 gene products (sig-HELPE6SH/
E7SH-kdel).
Achtergrond van het onderzoek
This is a phase I/II trial to evaluate the toxicity, immunogenicity and clinical response of two novel HPV DNA vaccines (sig-HELP-E6SH-kdel and sig-HELPE7SH-kdel), applied by DNA tattoo vaccination, in uVIN patients. This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies. The first cohort of patients (n=5) will be vaccinated with 2 mg of sig-HELP-E6SH/E7SH-kdel on days 0, 14, 28 and 42. Just before administration, 1 mg of sig-HELP-E6SH-kdel will be mixed with 1 mg of sig-HELP-E7SH-kdel to have 2 mg of the combined E6SH/E7SH. After all 5 patients received all vaccination, we will perform an interim analysis by flow cytometry. There are 2 possible scenarios after the interim analysis:
1. Acceptable immune response
2. Non acceptable immune response
Depending on the outcome of the interim analysis we will continue with the second cohort of patients.
1. Additional cohort of 9 patients
2. Termination of the trial
Doel van het onderzoek
This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies.
Onderzoeksopzet
Day -30 to 1: screening. Day 0: vaccination, PBMCs. Day 14: vaccination. Day 28: vaccination, PBMCs. Day 42: vaccination. Day 56: follow-uw, PBMC. Day 84: follow-up, PBMC. Month 3: follow-up, biopsy uVIN. Month 6: follow-up. Month 9: follow-up. Month 12: follow-up.
Onderzoeksproduct en/of interventie
This is a phase I/II trial to evaluate the toxicity, immunogenicity and clinical response of two novel HPV DNA vaccines (sig-HELP-E6SH-kdel and sig-HELPE7SH-kdel), applied by DNA tattoo vaccination, in uVIN patients. This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies. The first cohort of patients (n=5) will be vaccinated with 2 mg of sig-HELP-E6SH/E7SH-kdel on days 0, 14, 28 and 42. Just before administration, 1 mg of sig-HELP-E6SH-kdel will be mixed with 1 mg of sig-HELP-E7SH-kdel to have 2 mg of the combined E6SH/E7SH. After all 5 patients received all vaccination, we will perform an interim analysis by flow cytometry. There are 2 possible scenarios after the interim analysis:
1. Acceptable immune response
2. Non acceptable immune response
Depending on the outcome of the interim analysis we will continue with the second cohort of patients.
1. Additional cohort of 9 patients
2. Termination of the trial
Publiek
Jossie Rotman
Obstetrics & Gynecology/Immunotherapy Lab
Amsterdam
The Netherlands
(020-44)42175 Mob: +31622706702
Mail: j.rotman@vumc.nl
Wetenschappelijk
Jossie Rotman
Obstetrics & Gynecology/Immunotherapy Lab
Amsterdam
The Netherlands
(020-44)42175 Mob: +31622706702
Mail: j.rotman@vumc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
• Age above 18 years
• Willing and able to undergo the planned study procedures
• Written informed consent
• Histologically proven visible uVIN lesion (histology ≤3 months prior to enrolment and at
least 6 weeks after last treatment)
• HPV16-positive VIN lesion (to be determined on archival tumour tissue (≤10 years old); if
not available a new biopsy will be required)
• No indication of an active infectious disease: HIV, HCV and HBV negative
• No history of autoimmune disease or systematic undercurrent disease which might affect
immunocompetence
• Adequate bone marrow (WBC > 3.0/nL, platelets > 100/nL), renal function (creatinine
clearance > 40 mL/min), and liver function (bilirubin < 1.5 x ULN, normal blood
coagulation)
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
• Prior treatment with anti-HPV agents
• Participation in a study with another investigational drug within 30 days prior to enrolment
in this study
• Severe cardiac, respiratory, or metabolic disease
• Use of systemic steroids or other immunosuppressive drugs
• Use of oral anticoagulant drugs (except ascal)
• Severe infections requiring antibiotics
• Any treatment for the uVIN lesion within 6 weeks prior to the enrolment (including
imiquimod)
• Lactation or pregnancy (if applicable)
• Not willing to take adequate contraceptive measures (if applicable)
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7139 |
| NTR-old | NTR7337 |
| Ander register | HPV16 E6-E7 : N16SIG |