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

NCT03555422 | Completed Phase 3 DMC FDA Drug

• 4 other identifiers: KCP-330-024ENGOT-EN5BGOG-EN52017-000607-25
• Study Type: interventional
• Target: 263
• Locations: 10 countries
• Sites: 78

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

Keywords

Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases; Female

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Progression Free Survival: Assessed by Blinded Independent Central Review (BICR), per RECIST v1.1

  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 death from endometrial cancer (approximately 12 months after the last participant enrolled)

• Overall Survival (OS)

  Time from randomization until death (approximately 12 months after the last participant enrolled)

• Time to First Subsequent Treatment (TFST)

  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 second documented PD or death (approximately 12 months after the last participant enrolled)

Study Arms (2)

Selinexor

EXPERIMENTAL

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

Matching placebo for selinexor

PLACEBO COMPARATOR

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

Interventions

Selinexor 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

Selinexor

Matching placebo for selinexor 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

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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).

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead
• Belgian Gynaecological Oncology Group: collaborator
• Israeli Society of Gynecologic Oncology: collaborator
• Grupo Español de Investigación en Cáncer de Ovario: collaborator
• North Eastern German Society of Gynaecological Oncology: collaborator
• The Central and Eastern European Gynecologic Oncology Group: collaborator
• GOG Foundation: collaborator
• Multicenter Italian Trials in Ovarian Cancer (MITO): collaborator

Study Sites (78)

Arizona Oncology

Tucson, Arizona, 85711, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Florida Cancer Specialists (Sarah Cannon Research Institute)

West Palm Beach, Florida, 33401, United States

Location

Gynecological Cancer Institute of Chicago

Oak Lawn, Illinois, 60453, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

HCA Midwest Health - Kansas City (Sarah Cannon Research Institute)

Kansas City, Missouri, 64132, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Oklahoma Health Sciences Center - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oncology Associates of Oregon

Eugene, Oregon, 97401, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Tennessee Oncology Nashville (Sarah Cannon Research Institute)

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, Austin

Austin, Texas, 78731, United States

Location

Texas Oncology DFW

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Oncology DFW

Fort Worth, Texas, 76104, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

Jan Yperman Ziekenhuis

Ieper, 8900, Belgium

Location

Universitaire Ziekenhuizen K.U. Leuven

Leuven, 3000, Belgium

Location

CHU UCL Namur, Site Sainte-Elisabeth

Namur, 5000, Belgium

Location

AZ Turnhout

Turnhout, 2300, Belgium

Location

CHR Verviers

Verviers, 4800, Belgium

Location

London Health Sciences Centre (London Regional Cancer Centre)

London, Ontario, N6C 0A7, Canada

Location

University Health Network (PMCC)

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A 3J1, Canada

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150040, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Jiangxi Maternal and Child Health Hospital

Nanchang, Jiangxi, 330006, China

Location

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

Location

Chongqing University Cancer Hospital

Chongqing, Shapingba District, 400000, China

Location

Wenzhou Medical University - The First Affiliated Hospital

Wenzhou, Zhejiang, 325000, China

Location

University Hospital Brno

Brno, 60200, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

UH Královské Vinohrady

Prague, 10034, Czechia

Location

General University Hospital in Prague

Prague, 12851, Czechia

Location

Hospital Na Bulovce

Prague, 18081, Czechia

Location

Charite Berlin Universitatsmedizin

Berlin, 13353, Germany

Location

University Hospital Dresden

Dresden, 01307, Germany

Location

DIAKOVERE KH gGmbH, Henriettenstift Hannover

Hanover, 30171, Germany

Location

Universitatsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Universitätsfrauenklinik Mainz

Mainz, 55131, Germany

Location

Klinikum der Universitat Munchen

Munich, 80337, Germany

Location

Cartitas Klinikum Saarbrücken

Saarbrücken, 66113, Germany

Location

Universitätsfrauenklinik Ulm

Ulm, 89070, Germany

Location

Iaso Hospital

Marousi, Athens, 151 23, Greece

Location

ALEXANDRA Hospital

Athens, Greece, 11528, Greece

Location

Euromedica General Clinic

Thessaloniki, Macedonia, 54645, Greece

Location

Hillel Yaffe Medical Center

Hadera, 38100, Israel

Location

Wolfson Medical Center

Holon, 58100, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Istituto di Candiolo, FPO, IRCCS

Candiolo, 10060, Italy

Location

Romagnolo Scientific Institute for the Study and Treatment of Tumors

Meldola, 47014, Italy

Location

San Raffaele Hospital

Milan, 20132, Italy

Location

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

Milan, 20133, Italy

Location

ULSS 3 SERENISSIMA UOC Oncologia Ed Ematologia Oncologica

Mirano, 30174, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica

Naples, 80131, Italy

Location

Agostino Gemelli University Polyclinic Foundation

Rome, 30161, Italy

Location

Hospital Universitario Donostia

San Sebastián, Gipuzkoa, 20014, Spain

Location

Hospital Universitari Vall d' Hebrón

Barcelona, 08035, Spain

Location

Hospital Universitari Clínic de Barcelona

Barcelona, 08036, Spain

Location

Consorci Sanitari de Terrassa

Barcelona, 08227, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28220, Spain

Location

Hospital Universitario Infanta Sofía

Madrid, 28702, Spain

Location

Virgen de la Arrixaca University Clinical Hospital

Murcia, 30120, Spain

Location

Hospital Son Llàtzer

Palma, 071998, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario y Politécnico de La Fe

Valencia, 46026, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Related Publications (1)

• 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.

  PMID: 37669480 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases

Interventions

selinexor

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind placebo controlled study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: June 13, 2018
• Study Start: January 5, 2018
• Primary Completion: January 22, 2022
• Study Completion: April 3, 2025
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CA (3); DE (8); GR (3); IL (5); CZ (5); US (19); BE (6); CN (8); IT (7); ES (14)