Maintenance With Selinexor/Placebo After Combination Chemotherapy in Participants With Endometrial Cancer [SIENDO]

Endometrial Cancer Clinical Trial

— ENGOT-EN5  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03555422
• Other study ID #: KCP-330-024
• Secondary ID: ENGOT-EN5BGOG-EN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 5, 2018
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Karyopharm Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 263
• Est. completion date: December 2025
• Est. primary completion date: January 22, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

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
• 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

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Belgium	Jan Yperman Ziekenhuis	Ieper
Belgium	Universitaire Ziekenhuizen K.U. Leuven	Leuven
Belgium	CHU UCL Namur, Site Sainte-Elisabeth	Namur
Belgium	AZ Turnhout	Turnhout
Belgium	CHR Verviers	Verviers
Canada	London Health Sciences Centre (London Regional Cancer Centre)	London	Ontario
Canada	McGill University Health Centre (MUHC)	Montréal	Quebec
Canada	University Health Network (PMCC)	Toronto	Ontario
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Chongqing University Cancer Hospital	Chongqing	Shapingba District
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Jiangxi Maternal and Child Health Hospital	Nanchang	Jiangxi
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Wenzhou Medical University - The First Affiliated Hospital	Wenzhou	Zhejiang
China	Henan Cancer Hospital	Zhengzhou	Henan
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Ostrava	Ostrava
Czechia	General University Hospital in Prague	Prague
Czechia	Hospital Na Bulovce	Prague
Czechia	UH Královské Vinohrady	Prague
Germany	Charite Berlin Universitatsmedizin	Berlin
Germany	University Hospital Dresden	Dresden
Germany	DIAKOVERE KH gGmbH, Henriettenstift Hannover	Hannover
Germany	Universitatsklinikum Schleswig-Holstein	Kiel
Germany	Universitätsfrauenklinik Mainz	Mainz
Germany	Klinikum der Universitat Munchen	Munich
Germany	Cartitas Klinikum Saarbrücken	Saarbrücken
Germany	Universitätsfrauenklinik Ulm	Ulm
Greece	ALEXANDRA Hospital	Athens
Greece	Iaso Hospital	Maroussi	Athens
Greece	Euromedica General Clinic	Thessaloniki	Macedonia
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Wolfson Medical Center	Holon
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat -Gan
Italy	Istituto di Candiolo, FPO, IRCCS	Candiolo
Italy	Romagnolo Scientific Institute for the Study and Treatment of Tumors	Meldola
Italy	Istituto Nazionale dei Tumori IRCCS - MILANO S.C. Ginecologia Oncologica	Milan
Italy	San Raffaele Hospital	Milan
Italy	ULSS 3 SERENISSIMA UOC Oncologia Ed Ematologia Oncologica	Mirano
Italy	Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica	Naples
Italy	Agostino Gemelli University Polyclinic Foundation	Rome
Spain	Consorci Sanitari de Terrassa	Barcelona
Spain	Hospital Universitari Clínic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d' Hebrón	Barcelona
Spain	Hospital Universitario Infanta Sofi´a	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Virgen de la Arrixaca University Clinical Hospital	Murcia
Spain	Hospital Son Lla`tzer	Palma
Spain	Hospital Universitario Donostia	San Sebastián	Gipuzkoa
Spain	Hospital Universitario Virgen del Roci´o	Sevilla
Spain	Hospital Cli´nico Universitario de Valencia	Valencia
Spain	Hospital Universitario y Politécnico de La Fe	Valencia
Spain	Instituto Valenciano de Oncologi´a	Valencia
Spain	Hospital Cli´nico Universitario Lozano Blesa	Zaragoza
United States	Texas Oncology, Austin	Austin	Texas
United States	Texas Oncology DFW	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Oncology Associates of Oregon	Eugene	Oregon
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Texas Oncology DFW	Fort Worth	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	HCA Midwest Health - Kansas City (Sarah Cannon Research Institute)	Kansas City	Missouri
United States	Tennessee Oncology Nashville (Sarah Cannon Research Institute)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone	New York	New York
United States	Gynecological Cancer Institute of Chicago	Oak Lawn	Illinois
United States	University of Oklahoma Health Sciences Center - Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Stanford University	Palo Alto	California
United States	Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	Moffitt Cancer Center	Tampa	Florida
United States	Arizona Oncology	Tucson	Arizona
United States	Florida Cancer Specialists (Sarah Cannon Research Institute)	West Palm Beach	Florida

Sponsors (8)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc	Belgium and Luxembourg Gynaecological Oncology Group, GOG Foundation, Israeli Society of Gynecologic Oncology, Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies, North-Eastern German Society of Gynaecologic Oncology, Spanish Research Group in Ovarian Cancer, The Central and Eastern European Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  Czechia,  Germany,  Greece,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)