NCT04262089

Neo-adjuvant Pembrolizumab in dMMR/ POLE-EDM Uterine Cancer Patients: a Feasibility Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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 mutation)POLE-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 (n=10) and primary POLE-EDM UC (n=10) 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 endpoint).After 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 and/or 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.

Conditions

• Uterine Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab (Keytruda)	Pembrolizumab (Keytruda), 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.

Timeline

• Start date: 2020-11-01
• Primary completion: 2023-04-17
• Completion: 2023-11-01
• First posted: 2020-02-10
• Last updated: 2023-12-05

Locations

1 site across 1 country: Netherlands

Regulatory

• FDA-regulated drug study