Window of Opportunity Study of Pembrolizumab in Early Stage, High Grade Obesity-driven Endometrial Cancer
Status:
Recruiting
Trial end date:
2022-05-01
Target enrollment:
Participant gender:
Summary
Programmed cell death 1 (PD-1) inhibitor treatment may benefit patients with endometrial
cancer (EC) based on the following observations: 1) an overwhelming presence of PD-1 in ECs;
2) the well-known effect of obesity which activates pro-inflammatory white blood cells and
promotes the development of ECs; and 3) the high prevalence of a specific gene pattern (ie,
microsatellite instability hypermutated [MSI high]) among ECs that may be particularly
sensitive to this class of drugs. To identify potential biomarkers of response to PD-1
inhibitors in EC, we will conduct a window of opportunity study of pembrolizumab in 20
patients with clinical stage 1, grade 3 EC, encompassing endometrioid, serous and clear cell
histologies. Eligible patients will undergo a research biopsy for collection of fresh tissue
at the time of enrollment, in addition to the routinely performed endometrial biopsy that led
to the diagnosis of their cancer. Patients will receive a single dose of pembrolizumab (200
mg IV) prior to undergoing their scheduled hysterectomy with surgical staging three weeks
later. As per standard of care, adjuvant chemotherapy with paclitaxel and carboplatin will be
recommended after hysterectomy/surgical staging for women with endometrioid tumors and stage
III disease or women with serous/clear cell tumors at all stages of disease. However, in this
study pembrolizumab will be added to adjuvant paclitaxel and carboplatin for EC.
Pre-treatment endometrial biopsy specimens (fresh frozen tissue and formalin-fixed paraffin
embedded (FFPE)) and a post-treatment hysterectomy specimen (fresh frozen tissue and FFPE)
will be collected for translational studies. Blood, fecal and vaginal samples will be
collected pre-treatment, at the time of surgery and following 3 cycles of adjuvant
pembrolizumab/paclitaxel/carboplatin treatment.