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

NCT ID: NCT03555422

Last Updated: 2025-01-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 263 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-05
• Study Completion Date: 2025-12-31

Brief 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.

Conditions

Endometrial Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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

Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Group Type: PLACEBO_COMPARATOR

Matching placebo for selinexor

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Belgian Gynaecological Oncology Group

OTHER

Sponsor Role: collaborator

North-Eastern German Society of Gynaecologic Oncology

UNKNOWN

Sponsor Role: collaborator

Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies

UNKNOWN

Sponsor Role: collaborator

Spanish Research Group in Ovarian Cancer

UNKNOWN

Sponsor Role: collaborator

The Central and Eastern European Gynecologic Oncology Group

OTHER

Sponsor Role: collaborator

Israeli Society of Gynecologic Oncology

OTHER

Sponsor Role: collaborator

GOG Foundation

NETWORK

Sponsor Role: collaborator

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Oncology

Tucson, Arizona, United States

Stanford University

Palo Alto, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Florida Cancer Specialists (Sarah Cannon Research Institute)

West Palm Beach, Florida, United States

Gynecological Cancer Institute of Chicago

Oak Lawn, Illinois, United States

Parkview Research Center

Fort Wayne, Indiana, 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

NYU Langone

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Oklahoma Health Sciences Center - Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Oncology Associates of Oregon

Eugene, Oregon, United States

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Tennessee Oncology Nashville (Sarah Cannon Research Institute)

Nashville, Tennessee, 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

Texas Oncology DFW

Fort Worth, Texas, United States

VCU Massey Cancer Center

Richmond, Virginia, United States

UZ Gent

Ghent, , 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, , Belgium

London Health Sciences Centre (London Regional Cancer Centre)

London, Ontario, Canada

University Health Network (PMCC)

Toronto, Ontario, Canada

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Jiangxi Maternal and Child Health Hospital

Nanchang, Jiangxi, China

Liaoning Cancer Hospital

Shenyang, Liaoning, China

Chongqing University Cancer Hospital

Chongqing, Shapingba District, China

Wenzhou Medical University - The First Affiliated Hospital

Wenzhou, Zhejiang, China

University Hospital Brno

Brno, , Czechia

University Hospital Ostrava

Ostrava, , Czechia

UH Královské Vinohrady

Prague, , Czechia

General University Hospital in Prague

Prague, , Czechia

Hospital Na Bulovce

Prague, , Czechia

Charite Berlin Universitatsmedizin

Berlin, , Germany

University Hospital Dresden

Dresden, , Germany

DIAKOVERE KH gGmbH, Henriettenstift Hannover

Hanover, , Germany

Universitatsklinikum Schleswig-Holstein

Kiel, , Germany

Universitätsfrauenklinik Mainz

Mainz, , Germany

Klinikum der Universitat Munchen

Munich, , Germany

Cartitas Klinikum Saarbrücken

Saarbrücken, , Germany

Universitätsfrauenklinik Ulm

Ulm, , Germany

Iaso Hospital

Marousi, Athens, Greece

ALEXANDRA Hospital

Athens, Greece, Greece

Euromedica General Clinic

Thessaloniki, Macedonia, Greece

Hillel Yaffe Medical Center

Hadera, , Israel

Wolfson Medical Center

Holon, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Istituto di Candiolo, FPO, IRCCS

Candiolo, , Italy

Romagnolo Scientific Institute for the Study and Treatment of Tumors

Meldola, , Italy

San Raffaele Hospital

Milan, , Italy

Istituto Nazionale dei Tumori IRCCS - MILANO S.C. Ginecologia Oncologica

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, , Italy

Hospital Universitario Donostia

San Sebastián, Gipuzkoa, Spain

Hospital Universitari Vall d' Hebrón

Barcelona, , Spain

Hospital Universitari Clínic de Barcelona

Barcelona, , Spain

Consorci Sanitari de Terrassa

Barcelona, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, , Spain

Hospital Universitario Infanta Sofía

Madrid, , Spain

Virgen de la Arrixaca University Clinical Hospital

Murcia, , Spain

Hospital Son Llàtzer

Palma, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital Universitario y Politécnico de La Fe

Valencia, , Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Countries

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

References

Vergote I, Perez-Fidalgo JA, Hamilton EP, Valabrega G, Van Gorp T, Sehouli J, Cibula D, Levy T, Welch S, Richardson DL, Guerra EM, Scambia G, Henry S, Wimberger P, Miller DS, Klat J, Martinez-Garcia J, Raspagliesi F, Pothuri B, Romero I, Bergamini A, Slomovitz B, Schochter F, Hogdall E, Farinas-Madrid L, Monk BJ, Michel D, Kauffman MG, Shacham S, Mirza MR, Makker V; ENGOT-EN5/GOG-3055/SIENDO Investigators. Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer. J Clin Oncol. 2023 Dec 10;41(35):5400-5410. doi: 10.1200/JCO.22.02906. Epub 2023 Sep 5.

Reference Type: DERIVED

PMID: 37669480 (View on PubMed)

Other Identifiers

ENGOT-EN5

Identifier Type: OTHER

Identifier Source: secondary_id

BGOG-EN5

Identifier Type: OTHER

Identifier Source: secondary_id

2017-000607-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KCP-330-024

Identifier Type: -

Identifier Source: org_study_id