TY - JOUR
T1 - ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma
T2 - rationale, methods, and trial design
AU - Vergote, Ignace
AU - Perez Fidalgo, Alejandro
AU - Valabrega, Giorgio
AU - Monk, Bradley J
AU - Herzog, Thomas
AU - Cibula, David
AU - Colombo, Nicoletta
AU - Pothuri, Bhavana
AU - Sehouli, Jalid
AU - Korach, Jacob
AU - Barlin, Joyce
AU - Papadimitriou, Christos A
AU - van Gorp, Toon
AU - Richardson, Debra
AU - McCarthy, Michael
AU - Antill, Yoland
AU - Mirza, Mansoor Raza
AU - Li, Kai
AU - Kalyanapu, Pratheek
AU - Slomovitz, Brian
AU - Coleman, Robert L
N1 - © IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.
PY - 2024/8/5
Y1 - 2024/8/5
N2 - BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41).PRIMARY OBJECTIVE: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.STUDY HYPOTHESIS: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo.TRIAL DESIGN: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse.PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population.SAMPLE SIZE: A total of 220 patients will be enrolled.ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025.TRIAL REGISTRATION: NCT05611931.
AB - BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41).PRIMARY OBJECTIVE: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.STUDY HYPOTHESIS: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo.TRIAL DESIGN: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer.MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse.PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population.SAMPLE SIZE: A total of 220 patients will be enrolled.ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025.TRIAL REGISTRATION: NCT05611931.
KW - Uterine Cancer
KW - Clinical Trials, Phase III as Topic
KW - Double-Blind Method
KW - Hydrazines/administration & dosage
KW - Neoplasm Recurrence, Local/drug therapy
KW - Triazoles/administration & dosage
KW - Humans
KW - Endometrial Neoplasms/drug therapy
KW - Female
KW - Maintenance Chemotherapy/methods
KW - Tumor Suppressor Protein p53/genetics
UR - http://www.scopus.com/inward/record.url?scp=85191196733&partnerID=8YFLogxK
U2 - 10.1136/ijgc-2024-005412
DO - 10.1136/ijgc-2024-005412
M3 - Journal article
C2 - 38627035
SN - 1048-891X
VL - 34
SP - 1283
EP - 1289
JO - International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
JF - International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
IS - 8
ER -