CCTG EN10: A phase II study of tailored adjuvant therapy in POLE-mutated and p53-wildtype/NSMP early-stage endometrial cancer (EC)—RAINBO BLUE and TAPER.
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TPS5632 Background: Molecular classification of EC provides an opportunity to personalize treatment for patients with early disease based on prognosis. We hypothesize that de-escalated adjuvant treatment in patients with early-stage POLE-mutated ( POLEmut) or p53wt/NSMP (p53 wildtype/no specific molecular profile) EC is feasible and associated with favourable disease control, QOL and health economics. Methods: EN.10 is a Canadian Cancer Trials Group led phase II trial that enrolls two independent cohorts of patients with early stage EC based on tumour molecular status: POLEmut (substudy A) and p53wt/NSMP (substudy B). The primary objective is to estimate the 3-year rate of pelvic recurrence. Secondary objectives include estimated 3-year isolated vaginal recurrence, para-aortic recurrence, distant metastasis, survival (recurrence-free, EC-specific, overall survival) and to describe the patient decisional conflict and fear of recurrence. Tertiary objectives: QOL, economic evaluation and interrogation/discovery of additional prognostic biomarkers. Statistical Design: Registration to Substudy A or B is based on molecular classification. Treatment will be deescalated in both substudies; to surveillance-only (all early stage POLEmut, and a proportion of NSMP), or vaginal brachytherapy (proportion of NSMP), with NSMP stratification based on histological grade, and lymphovascular invasion. Substudy A can enroll endometrioid, serous, clear cell, un/dedifferentiated and carcinosarcomas whereas Substudy B is confined to endometrioid histotype. Both arms require ECOG 0-2 and hysterectomy+BSO with nodal assessment required for stage II and grade 3 EC. A total of 120 patients with POLEmut (Sub-study A) and 180 with p53wt/NSMP ER+ (Sub-study B) EC will be recruited in 3 years. If the upper 95% confidence limit is less than 5% in either of Substudy A, Cohort A1 and Sub-study B or both, it will be concluded that patients in one or both groups have an acceptable low risk of pelvic recurrence at 3 years with molecularly-tailored de-escalated adjuvant treatment An additional estimated 25 patients with higher risk POLEmut EC will be enrolled for an exploratory analysis. Conduct to Date: Study activation Dec 19 2022. Enrollment January 31, 2023: 36 Supported by Canadian Cancer Society, Canadian Institutes of Health Research, Gynecologic Cancer Initiative, BC Cancer Foundation. Clinical trial information: NCT05640999 .
