Ignite Creation Date:
2024-05-06 @ 2:15 PM
Last Modification Date:
2024-10-26 @ 1:27 PM
Study NCT ID:
NCT04262089
Status:
COMPLETED
Last Update Posted:
2023-12-05
First Post:
2020-01-28
Brief Title:
Neo-adjuvant Pembrolizumab in dMMR POLE-EDM Uterine Cancer Patients a Feasibility Study
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
Neo-adjuvant Pembrolizumab in dMMR POLE-EDM Uterine Cancer Patients a Feasibility Study
Status:
COMPLETED
Status Verified Date:
2023-12
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:
PAM
Brief Summary:
In this feasibility study the investigators intend to treat patients with high mutational uterine cancer with two cycles immune checkpoint inhibition before standard-of-care hysterectomy
Detailed Description:
Objective
The investigators aim to establish proof-of-concept for use of immune checkpoint blockade ICB as novel neo-adjuvant therapy in deficient mismatch repair dMMR and Polymerase ε mutationPOLE-EDM uterine cancer UC When ICB proves to be feasible as defined in the primary endpoint a follow-up with a larger multicenter studies to determine clinical efficacy such as postponing standard-of-care surgery or randomized studies to standard-of-care
Study design
The investigators planned a window-of-opportunity study of ICB in primary dMMR UC n10 and primary POLE-EDM UC n10 patients ICB pembrolizumab anti-PD1 will be administered in two cycles of 3 weeks between diagnosis and standard-of-care hysterectomy
Tumor responses to pembrolizumab will be assessed 3 weeks after the second cycle of pembrolizumab by a pathologist primary endpoint and MRI secondary endpointAfter treatment with immun checkpoint blockade a hysterectomy will take place standard-of care Peripheral blood and tumor samples will be used to evaluate immune responses
Study population
Primary dMMR POLE-EDM UC patients of any stage andor grade who are intended to be treated with a hysterectomy recruited from the North-Netherlands oncological region
Intervention Pembrolizumab 200mg IV Q3W for a total of 2 administrations per patient integrated into standard-of-care protocol prior to surgery Based on the well-established time lines the interval between diagnosis and standard of care hysterectomy is sufficient to treat patients with two cycles of pembrolizumab without interfering with standard of care
Main study endpoints
The primary endpoint is the response rate of the tumor assessed by pathology in uterine cancer patients treated with neo-adjuvant pembrolizumab The secondary endpoint is the objective response rate of the tumor by MRI using RECIST Exploratory objectives are immunogenicity safety and the value of a pipelle biopsy as a predictor for response
The investigators aim to establish proof-of-concept for use of immune checkpoint blockade ICB as novel neo-adjuvant therapy in deficient mismatch repair dMMR and Polymerase ε mutationPOLE-EDM uterine cancer UC When ICB proves to be feasible as defined in the primary endpoint a follow-up with a larger multicenter studies to determine clinical efficacy such as postponing standard-of-care surgery or randomized studies to standard-of-care
Study design
The investigators planned a window-of-opportunity study of ICB in primary dMMR UC n10 and primary POLE-EDM UC n10 patients ICB pembrolizumab anti-PD1 will be administered in two cycles of 3 weeks between diagnosis and standard-of-care hysterectomy
Tumor responses to pembrolizumab will be assessed 3 weeks after the second cycle of pembrolizumab by a pathologist primary endpoint and MRI secondary endpointAfter treatment with immun checkpoint blockade a hysterectomy will take place standard-of care Peripheral blood and tumor samples will be used to evaluate immune responses
Study population
Primary dMMR POLE-EDM UC patients of any stage andor grade who are intended to be treated with a hysterectomy recruited from the North-Netherlands oncological region
Intervention Pembrolizumab 200mg IV Q3W for a total of 2 administrations per patient integrated into standard-of-care protocol prior to surgery Based on the well-established time lines the interval between diagnosis and standard of care hysterectomy is sufficient to treat patients with two cycles of pembrolizumab without interfering with standard of care
Main study endpoints
The primary endpoint is the response rate of the tumor assessed by pathology in uterine cancer patients treated with neo-adjuvant pembrolizumab The secondary endpoint is the objective response rate of the tumor by MRI using RECIST Exploratory objectives are immunogenicity safety and the value of a pipelle biopsy as a predictor for response
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None