Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma

Endometrial Cancer Clinical Trial

— XPORT-EC-042  

Official title:

A Phase 3, 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05611931
• Other study ID #: XPORT-EC-042
• Secondary ID: GOG-3083ENGOT-EN
• Status: Recruiting
• Phase: Phase 3
• Start date: April 18, 2023
• Est. completion date: January 31, 2028

Study information

• Verified date: June 2024
• Source: Karyopharm Therapeutics Inc
• Contact: Karyopharm Medical Information
• Phone: (888) 209-9326
• Email: clinicaltrials[@]karyopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v 1.1]) after completing at least 12 weeks of platinum-based therapy. A total of 220 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: January 31, 2028
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At least 18 years of age at the time of signing informed consent.

• Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinosarcoma.

• TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.

• Completed a single line, at least 12 weeks of platinum-based therapy (not including adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed partial or complete response (PR or CR) by imaging, according to RECIST version 1.1. The participants should have received treatment for:

Primary Stage IV disease, defined as:

• had a primary or later debulking surgery during first-line platinum-based therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR

• had a primary or later debulking surgery during first-line platinum-based therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease) and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR

• had no surgery and achieved PR or CR after at least 12 weeks platinum-based chemotherapy

OR

At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy and/or immunotherapy 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 platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse,

• 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 platinum-based 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 platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse.

• Previous treatment with anti-programmed cell death protein 1(PD-1) or anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant biologic agents (e.g., bevacizumab, trastuzumab) is allowed.

• Must be able to initiate study drug 3 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 less than (<) 3*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

• Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or equal to (>=) 1.5*10^9/liter (L); platelet count >= 100*10^9/L; hemoglobin >= 9.0 gram per deciliter (g/dL) per local laboratory results

• Renal function: estimated creatinine clearance (CrCl) of >= 20 milliliter per minute (mL/min), calculated using the standard local formula, as applicable

• In the opinion of the Investigator, the participant must:

• Have a life expectancy of at least 12 weeks, and

• Be fit to receive investigational 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 90 days following the last dose of study drug.

• Written informed consent signed in accordance with federal, local, and institutional guidelines prior to the first screening procedure.

Exclusion Criteria:

• Participants meeting any of the following exclusion criteria are not eligible to enroll in this study:

• Has any uterine sarcomas (carcinosarcomas - not excluded), clear cell or small cell carcinoma with neuroendocrine differentiation

• Received a blood or platelet transfusion during the 2 weeks prior to Cycle 1 Day 1 (C1D1). Participants' hemoglobin must be assessed within 2 weeks of screening and at least 1 week post transfusion

• Concurrent systemic steroid therapy higher than physiologic dose (> 10 milligram per day [mg/day] of prednisone or equivalent). Systemic steroid therapy as pre-medication for taxane is allowed

• Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:

• Not recovered from major surgery <= 28 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted

• Having ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade > 1, with the exception of alopecia. In specific cases, participants whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor

• Palliative radiotherapy within 14 days of the intended C1D1. Palliative radiotherapy may be permitted for symptomatic control of pain from bone metastases, provided that the radiotherapy does not involve target lesions, and the reason for the radiotherapy does not reflect evidence of disease progression.

• Any gastrointestinal dysfunctions that could interfere with the absorption of selinexor (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 > grade 1).

• Participants unable to tolerate two forms of antiemetics for at least 2 cycles will not be eligible for the trial.

• Active, ongoing or uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of screening.

• Serious psychiatric or medical condition that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous.

• Previous treatment with an XPO1 inhibitor.

• Stable disease or PD on the post-chemotherapy scan or clinical evidence of progression prior to randomization.

• Participants who received any systemic anticancer therapy including investigational agents <= 3 weeks (or <= 5 half-lives of the drug [whichever is shorter]) prior to C1D1.

• Major injuries or surgery within 14 days prior to C1D1 and/or planned major surgery during the on-treatment study period.

• Other malignant disease with disease-free <= 3 years except: curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma in situ (DCIS) of the breast.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor, or other agents used in the study.

• Active brain metastases (e.g., stable for < 8 weeks, no adequate previous treatment with radiotherapy and/or surgery, symptomatic, requiring treatment with anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose for at least 1 month before randomization).

• Females who are pregnant or lactating.

• Any other life-threatening illness, active medical condition, organ system dysfunction, or serious active psychiatric issue which, in the Investigator's opinion, could compromise the participant's safety or the participant's ability to remain compliant with study procedures.

Related Conditions & MeSH terms

• Carcinoma
• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• Selinexor
Dose: 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral
• Matching Placebo for selinexor
Dose:60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral

Locations

Country	Name	City	State
Australia	Border Medical Oncology and Haematology	Albury East	New South Wales
Australia	Box Hill Hospital - Eastern Health (Oncology)	Box Hill	Victoria
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Monash Health	Clayton	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Central Coast LHD - Gosford & Wyong Hospitals	Gosford	New South Wales
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Cabrini Health	Malvern	Victoria
Australia	Peter MacCallum Cancer Centre/RWH/RMH	Melbourne	Victoria
Australia	Newcastle Private Hospital	New Lambton Heights	New South Wales
Australia	ICON Cancer Centre Southport	Southport	Queensland
Australia	The Royal Adelaide Hospital	Southport
Australia	Toowoomba Hospital	Toowoomba	Queensland
Australia	Westmead Hospital	Wentworthville	New South Wales
Belgium	Cliniques Universitaires St. Luc	Bruxelles
Belgium	AZ Sint Lucas	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHU Ambroise Pare	Mons
Belgium	CHU UCL Namur, Site Sainte-Elisabeth	Namur
Canada	Nova Scotia Health / QEII Health Sciences Centre / Atlantic Clinical Cancer Research Unit	Halifax	Nova Scotia
Canada	Centre Hospitalier de l'Université de Montréal	Montreal	Quebec
Canada	McGill University Health Centre (MUHC)	Montréal	Quebec
Canada	Princess Margaret	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
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
Georgia	High Technology Hospital Medcenter	Batumi
Georgia	Caucasus Medical Centre	Tbilisi
Georgia	LTD Innova Medical Center	Tbilisi
Georgia	Multiprofile Clinic "Consilium Medulla"	Tbilisi
Georgia	Tbilisi Cancer Center	Tbilisi
Germany	Charite Berlin Universitatsmedizin	Berlin
Germany	KEM | Evang. Kliniken Essen-Mitte, Evang. Huyssens-Stiftung Essen-Huttrop	Essen
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitatsklinikum Schleswig-Holstein	Kiel
Germany	University Hospital Dresden	Kiel
Germany	Universitätsklinikum Köln	Koln
Germany	Helios Klinikum Krefeld	Krefeld
Germany	Universitätsklinik Leipzig	Liepzig
Germany	Universitätsfrauenklinik Mainz	Mainz
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Klinik und Poliklinik fur Frauenheilkunde und Geburtshilfe GroBhadern	Munich
Germany	Klinikum Südstadt Rostock	Rostock
Germany	Universitätsfrauenklinik Ulm	Ulm
Greece	ALEXANDRA Hospital	Athens
Greece	Hygeia Hospital	Athens
Greece	IASO Hospital	Maroúsi	Athens
Greece	Euromedica General Clinic	Thessaloníki
Hungary	Unit of Gynecol.Oncol., Dept.Obstet.Gynecol., Clinical Center, University of Debrecen	Debrecen
Hungary	Petz Aladár University Teaching Hospital	Gyor
Ireland	Cork University Hospital	Cork
Ireland	Beacon Hospital Research Institute	Dublin
Ireland	St. James Hospital	Dublin
Ireland	Galway University	Galway
Ireland	University Hospital Waterford	Waterford
Israel	Hillel-Yaffe Medical Center	Hadera
Israel	Wolfson Medical Center	Holon
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Italy	IRCCS Azienda Ospedaliero Universitaria di Bologna	Bologna
Italy	ASST Spedali Civili Di Brescia	Brescia
Italy	IRCCS Istituto Romagnolo Per Lo Studio Del Tumori "Dino Amadori" - IRST S.R.L.	Meldola
Italy	San Raffaele Hospital	Milan
Italy	Instituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale dei Tumori IRCCS - MILANO S. C. Ginecologia Oncologica	Milano
Italy	Ospedale San Gerardo - Asst Monza	Monza
Italy	"Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica"	Napoli
Italy	Istituto Oncologico Veneto	Padova
Italy	Universita di Pisa	Pisa
Italy	Nuovo Ospedale di Prato	Prato
Italy	Fondazione Policlinico Universitario Agostino Gemelli - ROMA	Roma
Italy	IRCCS Istituto Clinico Humanitas	Rozzano
Italy	AO Ordine Mauriziano	Torino
Italy	Ospedale Ostetrico Ginecologico Sant'Anna	Torino
Slovakia	National Cancer Institute	Bratislava
Slovakia	St. Elisabeth Cancer Institute	Bratislava
Slovakia	UH Trencín	Trencín
Spain	ICO Badalona	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d' Hebrón	Barcelona
Spain	Institut Catala d'Oncologia Hospitalet	Barcelona
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario Reina Sofía	Córdoba	Andalucia
Spain	Virgen de la Arrixaca University Clinical Hospital	El Palmar Murcia
Spain	Hospital Universitario Donostia	Gipuzkoa
Spain	Institut Catala d'Oncologia de Girona	Girona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	H 12 de Octubre	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Universitatrio Virgen de la Victoria	Málaga
Spain	Hospital Universitario Virgen del Roci´o	Sevilla
Spain	Hospital Cli´nico Universitario de Valencia	Valencia
Spain	Hospital LaFe Uacenlia	Valencia
Spain	Instituto Valenciano de Oncologi´a	Valencia
Spain	Hospital Cli´nico Universitario Lozano Blesa	Zaragoza
United States	Women's Cancer Care Associates, LLC	Albany	New York
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Emory University	Atlanta	Georgia
United States	Grady Hospital	Atlanta	Georgia
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	Our Lady of the Lake Hospital, Inc.	Baton Rouge	Louisiana
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Atrium Health Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Chattanooga's Program in Women's Oncology	Chattanooga	Tennessee
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Zangmeister Cancer Center	Columbus	Ohio
United States	Parkland Health & Hospital System	Dallas	Texas
United States	Texas Oncology - Dallas	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke Cancer Center	Durham	North Carolina
United States	Oncology Associates of Oregon	Eugene	Oregon
United States	NorthShore University Health System	Evanston	Illinois
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Texas Oncology - Fort Worth	Fort Worth	Texas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	The West Clinic, PLLC dba West Cancer Center	Germantown	Tennessee
United States	Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	University of Colorado Cancer Center	Highlands Ranch	Colorado
United States	Houston Methodist	Houston	Texas
United States	St Vincent Hospital	Indianapolis	Indiana
United States	St. Dominic's Gynecologic Oncology	Jackson	Mississippi
United States	Midwest Ventures Group HCA MId America Division	Kansas City	Missouri
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Long Beach Memorial Medical Center	Los Angeles	California
United States	UCLA - Women's Health Clinical Research Unit	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical College of Wisconsin/ Freodtert Hospital	Milwaukee	Wisconsin
United States	NYU Langone Hospital-Long Island	Mineola	New York
United States	LSU Health Sciences Center New Orleans	New Orleans	Louisiana
United States	Mount Sinai	New York	New York
United States	Mount Sinai Chelsea	New York	New York
United States	Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UC Irvine	Orange	California
United States	Stanford University	Palo Alto	California
United States	Honor Health	Phoenix	Arizona
United States	Allegheny Health Network - West Penn Hospital	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Center Of Hope	Reno	Nevada
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Oncology - San Antonio	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California
United States	Trials365, LLC	Shreveport	Louisiana
United States	Avera	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Texas Oncology - The Woodlands	The Woodlands	Texas
United States	Texas Oncology, PC, Tyler	Tyler	Texas

Sponsors (10)

Lead Sponsor

Collaborator

Karyopharm Therapeutics Inc

Australia New Zealand Gynaecological Oncology Group, Belgium and Luxembourg Gynaecological Oncology Group, European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation, Israeli Society of Gynecologic Oncology, Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies, North Eastern German Society of Gynaecological Oncology, Spanish Research Group in Ovarian Cancer, The Central and Eastern European Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Georgia,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Assessed by Investigator as per RECIST v1.1		Time from randomization until disease progression (PD) or death, whichever occurs first (up to 34 months)
Secondary	Overall Survival (OS)		Up to 34 months
Secondary	Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs		From start of study drug administration up to 34 months
Secondary	Number of Participants with Clinically Significant Changes in Clinical Laboratory Values, Vital Signs and Physical Examination Reported as an Adverse Event		From start of study drug administration up to 34 months
Secondary	Number of Participants With Severity of Adverse Event According to Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0		From start of study drug administration up to 34 months
Secondary	Time to First Subsequent Therapy (TFST)		Time from randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first (up to 34 months)
Secondary	Time to Second Subsequent Therapy (TSST)		Time from randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first (up to 34 months)
Secondary	Progression-free Survival After Consecutive Treatment (PFS2)		Time from randomization until the second progression event or death due to any cause, whichever occurs first (up to 34 months)
Secondary	Progression-free Survival (PFS) Assessed by a Blinded Independent Central Review (BICR), per RECIST v1.1		Time from randomization until PD or death, whichever occurs first (up to 34 months)
Secondary	European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)	EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline up to 34 months