Ignite Creation Date:
2024-05-06 @ 7:27 PM
Last Modification Date:
2024-10-26 @ 3:07 PM
Study NCT ID:
NCT06015854
Status:
RECRUITING
Last Update Posted:
2023-08-29
First Post:
2023-08-23
Brief Title:
Vvax001 Cancer Vaccine in Premalignant Cervical Lesions - Phase II
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Vvax
Brief 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 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 andor incompetence which may lead to infertility and partus prematurisimmaturis 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-E67-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
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-E67-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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None