Maintenance With Selinexor/Placebo After Combination Chemotherapy in Participants With Endometrial Cancer [SIENDO] (ENGOT-EN5)

A Randomized, Double-Blind, Phase 3 Trial of Maintenance With Selinexor/ Placebo After Combination Chemotherapy for Patients With Advanced or Recurrent Endometrial Cancer

This is a prospective, multicenter, double-blind, placebo-controlled, randomized Phase 3 study. The purpose of the study is to obtain evidence of efficacy for maintenance selinexor in participants with advanced or recurrent endometrial cancer. Participants with primary stage IV or recurrent disease who are in partial or complete response after having completed a single line of at least 12 weeks of taxane-platinum combo therapy will be randomized in a 2:1 manner to maintenance therapy with 80 milligram (mg) with selinexor once weekly (QW) or placebo until progression.

Study Overview

• Status: Active, not recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Selinexor; Drug: Matching placebo for selinexor

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Ieper, Belgium, 8900
    • Jan Yperman ziekenhuis
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen K.U. Leuven
  • Namur, Belgium, 5000
    • CHU UCL Namur, Site Sainte-Elisabeth
  • Turnhout, Belgium, 2300
    • Az Turnhout
  • Verviers, Belgium, 4800
    • CHR Verviers
• Canada
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • London Health Sciences Centre (London Regional Cancer Centre)
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network (PMCC)
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre (MUHC)
• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150040
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Maternal and Child Health Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital
  • Shapingba District
    • Chongqing, Shapingba District, China, 400000
      • Chongqing University Cancer Hospital
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Wenzhou Medical University - The First Affiliated Hospital
• Czechia
  • Brno, Czechia, 60200
    • University Hospital Brno
  • Ostrava, Czechia, 70852
    • University Hospital Ostrava
  • Prague, Czechia, 10034
    • UH Královské Vinohrady
  • Prague, Czechia, 12851
    • General University Hospital in Prague
  • Prague, Czechia, 18081
    • Hospital Na Bulovce
• Germany
  • Berlin, Germany, 13353
    • Charite Berlin Universitatsmedizin
  • Dresden, Germany, 01307
    • University Hospital Dresden
  • Hannover, Germany, 30171
    • DIAKOVERE KH gGmbH, Henriettenstift Hannover
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein
  • Mainz, Germany, 55131
    • Universitätsfrauenklinik Mainz
  • Munich, Germany, 80337
    • Klinikum der Universität München
  • Saarbrücken, Germany, 66113
    • Cartitas Klinikum Saarbrücken
  • Ulm, Germany, 89070
    • Universitätsfrauenklinik Ulm
• Greece
  • Athens, Greece, 11528
    • Alexandra Hospital
  • Athens
    • Maroussi, Athens, Greece, 151 23
      • Iaso Hospital
  • Macedonia
    • Thessaloniki, Macedonia, Greece, 54645
      • Euromedica General Clinic
• Israel
  • Hadera, Israel, 38100
    • Hillel Yaffe Medical Center
  • Holon, Israel, 58100
    • Wolfson Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center
  • Ramat -Gan, Israel, 52621
    • Sheba Medical Center
• Italy
  • Candiolo, Italy, 10060
    • Istituto di Candiolo, FPO, IRCCS
  • Meldola, Italy, 47014
    • Romagnolo Scientific Institute for the Study and Treatment of Tumors
  • Milan, Italy, 20132
    • San Raffaele Hospital
  • Milan, Italy, 20133
    • Istituto Nazionale dei Tumori IRCCS - MILANO S.C. Ginecologia Oncologica
  • Mirano, Italy, 30174
    • ULSS 3 SERENISSIMA UOC Oncologia Ed Ematologia Oncologica
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica
  • Rome, Italy, 30161
    • Agostino Gemelli University Polyclinic Foundation
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d' Hebron
  • Barcelona, Spain, 08036
    • Hospital Universitari Clínic de Barcelona
  • Barcelona, Spain, 08227
    • Consorci Sanitari de Terrassa
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28702
    • Hospital Universitario Infanta Sofía
  • Madrid, Spain, 28220
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Murcia, Spain, 30120
    • Virgen de la Arrixaca University Clinical Hospital
  • Palma, Spain, 071998
    • Hospital Son Llatzer
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncología
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico de La Fe
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano Blesa
  • Gipuzkoa
    • San Sebastián, Gipuzkoa, Spain, 20014
      • Hospital Universitario Donostia
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists (Sarah Cannon Research Institute)
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Gynecological Cancer Institute of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Health - Kansas City (Sarah Cannon Research Institute)
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Langone
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center - Stephenson Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital of Rhode Island
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology Nashville (Sarah Cannon Research Institute)
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology, Austin
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology, Dallas
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology Forth Worth
  • Virginia
    • Richmond, Virginia, United States, 23298
      • VCU Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female, at least 18 years of age at the time of informed consent.
• Histological confirmed endometrial cancer of the endometrioid, serous, or undifferentiated type. Carcinosarcoma of the uterus is also allowed.
• Completed a single line of at least 12 weeks of taxane-platinum combination therapy (not including adjuvant or neoadjuvant therapy), and achieved partial remission (PR) or complete remission (CR) according to RECIST version 1.1 for:
• Primary Stage IV disease, defined as:
• had a primary or later debulking surgery during first-line taxane-platinum therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks taxane-platinum chemotherapy, OR
• had a primary or later debulking surgery during first-line taxane-platinum therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease,) and achieved PR or CR after at least 12 weeks taxane-platinum chemotherapy, OR
• had no surgery and achieved PR or CR after at least 12 weeks taxane-platinum chemotherapy.

OR

• At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy therapy for Stage I-IV disease), defined as:
• had Stage I-III disease at diagnosis and received at initial diagnosis adjuvant chemotherapy and relapsed later. Participants should have PR or CR after at least 12 weeks of taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
• had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at initial diagnosis and relapsed later. Participants should have PR or CR after at least 12 weeks of taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
• had Stage IV disease at diagnosis and received initially chemotherapy with or without surgery and relapsed later. At the time of relapse, participants should have PR or CR after at least 12 weeks of taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse.

Participants that required their chemotherapy dose held during the 12-week therapy may be considered if they meet the other criteria above and achieve PR or CR per RECIST V1.1.

• Must be able to initiate study drug 5 to 8 weeks after completion of their final dose of chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participants must have adequate bone marrow function and organ function within 2 weeks before starting study drug as defined by the following laboratory criteria:
• Hepatic function: total bilirubin up to 1.5*upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (≤) 2.5*ULN in participants without liver metastasis. For participants with known liver involvement of their tumor: AST and ALT ≤5*ULN.
• Hematopoetic function: Absolute neutrophil count (ANC) greater than or equal to (≥) 1.5*10^9/L; platelet count ≥100*10^9 per liter (/L); hemoglobin ≥9.0 gram per deciliter (g/dL).
• Renal function: estimated creatinine clearance (CrCl) of ≥20 milliliter per minute (mL/min), calculated using the Cockroft Gault formula.
• In the opinion of the Investigator, the participant must:
• Have a life expectancy of at least 12 weeks, and
• Be fit to receive experimental therapy.
• Premenopausal females of childbearing potential must have a negative pregnancy test (serum β-human chorionic gonadotropin test) prior to the first dose of study drug. Female participants of childbearing potential must agree to use highly effective methods of contraception throughout the study and for 1 week following the last dose of study drug.
• Written informed consent in accordance with federal, local, and institutional guidelines. The participant must provide informed consent prior to the first Screening procedure.

Exclusion Criteria:

• Has any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear cell carcinomas.
• Received a blood or platelet transfusion during 4 weeks prior to randomization.
• Being treated with a concurrent cancer therapy.
• Previous treatment with an exportin 1 (XPO1) inhibitor.
• Previous treatment with anti- programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) immunotherapy (e.g., pembrolizumab).
• Concurrent treatment with an investigational agent or participation in another clinical trial.
• Participants who received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to cycle 1 day 1 (C1D1). Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases in extremities, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect progressive disease (PD).
• Major injuries or surgery within 14 days prior to C1D1 and/or planned surgery during the on-treatment study period.
• Previous malignant disease, except participants with other malignant disease, for which the participant has been disease-free for at least 3 years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
• Any life-threatening illness, medical condition or organ system dysfunction, which, in the investigator's opinion, could compromise the participant's safety or compliance with the protocol.
• Known contraindications to selinexor.
• Known uncontrolled hypersensitivity to the investigational drug, or to its excipients.
• Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
• Persistent Grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, with the exception of alopecia.
• Active brain metastases (e.g., stable for <8 weeks, no adequate previous treatment with radiotherapy and/or surgery, symptomatic, requiring treatment with anti-convulsants. Corticoid therapy is allowed if administered as stable dose for at least 1 month before randomization).
• Known unstable cardiovascular function:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block /right bundle branch block will not be excluded), or
• Congestive heart failure of New York Heart Association Class ≥3, or
• Myocardial infarction within 3 months
• Females who are pregnant or actively breastfeeding.
• Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
• Active hepatitis C and/or B infection.
• Participants unable to swallow tablets, participants with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study drug. A history of bowel obstruction requiring a nasogastric tube or intravenous infusion during the past 2 months is not allowed (except when this obstruction is caused by surgery or other non-malignant causes).
• Psychiatric illness or substance use that would prevent the participant from giving informed consent or being compliant with the study procedures.
• Participants unwilling or unable to comply with the protocol.
• Persons who have been committed to an institution by official or judicial order.
• Participants with dependency on the Sponsor, Investigator or study site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selinexor; Participants will receive fixed dose of selinexor 80 mg (or 60 mg for participants with a body mass index [BMI] less than [<] 20 kilogram per meter square [kg/m^2]) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.	Drug: Selinexor; Dose: 80 mg (4 tablets) or 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral
Placebo Comparator: Matching placebo for selinexor; Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.	Drug: Matching placebo for selinexor; Dose: 80 mg (4 tablets) or 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Compare progression free survival of the two treatment arms as assessed by the investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.	Time from randomization until disease progression (PD) or death, whichever occurs first (approximately 12 months after the last participant enrolled)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival: Assessed by Blinded Independent Central Review (BICR), per RECIST v1.1	Time from randomization until documented PD or death due to any cause, whichever occurs first. Documented PD will be based on BICR assessments.	Time from randomization until PD or death, whichever occurs first (approximately 12 months after the last participant enrolled)
Disease Specific Survival (DSS)	Time from randomization until date of death from endometrial cancer.	Time from randomization until death from endometrial cancer (approximately 12 months after the last participant enrolled)
Overall Survival (OS)	Time from randomization until date of death from any cause.	Time from randomization until death (approximately 12 months after the last participant enrolled)
Time to First Subsequent Treatment (TFST)	Time from randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first.	Time from randomization until first therapy initiation after discontinuation of study drug or death, whichever occurs first (approximately 12 months after the last participant enrolled)
Progression-free Survival After Subsequent Treatment (PFS2)	Time from randomization until the second documented disease progression or death due to any cause by any cause on any subsequent line of anticancer therapy.	Time from randomization until second documented PD or death (approximately 12 months after the last participant enrolled)
Time to Second Subsequent Treatment (TSST)	Time from randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first.	Time from randomization until second therapy initiation after discontinuation of study drug or death, whichever occurs first (approximately 12 months after the last participant enrolled)
Disease Control Rate (DCR)	Best response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) among patients with PR as best response to prior chemotherapy.	Time from randomization up to approximately 16 weeks
Health-Related Quality of Life (HR-QoL): Measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30	Patient-reported outcomes will be measured by the EORTC QLQ C30 questionnaire.	Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled)
Health-Related Quality of Life: Measured by EORTC QLQ-EN24	Patient-reported outcomes will be measured by the EORTC QLQ-EN24 questionnaire.	Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled)
Health-Related Quality of Life: Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)	Patient-reported outcomes will be measured by the EORTC EQ-5D-5L.	Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled)
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Occurrence, Nature, and Severity of AEs		From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled)
Number of Participants with Significant Physical Examination, Clinical Laboratory, and Vital Signs Results		From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled)

Collaborators and Investigators

• Sponsor: Karyopharm Therapeutics Inc
• Collaborators: Belgium and Luxembourg Gynaecological Oncology Group; North-Eastern German Society of Gynaecologic Oncology; Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies; Spanish Research Group in Ovarian Cancer; The Central and Eastern European Gynecologic Oncology Group; Israel Society of Gynecologic Oncology; The GOG Foundation, Inc.
• Investigators: Study Director: Michael Kauffman, MD, PhD, Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Neoplasms; Female; Neoplasms by Site; Genital Neoplasms; Uterine Neoplasms; Endometrial Neoplasms; Uterine Diseases; Genital Diseases
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms
• Other Study ID Numbers: KCP-330-024; ENGOT-EN5 (Other Identifier: European Network of Gynaecological Oncological Trial Groups); BGOG-EN5 (Other Identifier: Belgium and Luxembourg Gynaecological Oncology Group); 2017-000607-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No