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

Phase 3

Recruiting

• Conditions: Endometrial Cancer
• Interventions: Drug: Matching Placebo for selinexor; Drug: Selinexor

• Registration Number: NCT05611931
• Lead Sponsor: Karyopharm Therapeutics Inc

Brief 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 th...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2022-11-03
• Study First Submitted QC: 2022-11-03
• Study First Posted: 2022-11-10
• Study Start: 2023-04-18
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-23
• Last Update Posted: 2024-07-24
• Primary Completion: 2025-01-31
• Study Completion: 2028-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

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 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 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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Selinexor	Selinexor	Participants will receive a fixed dose of selinexor 60 milligrams (mg) oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	From start of study drug administration up to 34 months
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
Overall Survival (OS)	Up to 34 months
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
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)
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)
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)
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)	Baseline up to 34 months	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 "healt...
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)

Trial Locations

Locations (166)

The University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Honor Health; 🇺🇸 Phoenix, Arizona, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

City of Hope at Irvine Lennar; 🇺🇸 Irvine, California, United States

UCLA - Women's Health Clinical Research Unit; 🇺🇸 Los Angeles, California, United States

Long Beach Memorial Medical Center; 🇺🇸 Los Angeles, California, United States

UC Irvine; 🇺🇸 Orange, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Highlands Ranch Hospital; 🇺🇸 Highlands Ranch, Colorado, United States

University of Colorado Cancer Center; 🇺🇸 Highlands Ranch, Colorado, United States

Broward Health Medical Center; 🇺🇸 Fort Lauderdale, Florida, United States

Mount Sinai Comprehensive Cancer Center; 🇺🇸 Miami Beach, Florida, United States

Grady Hospital; 🇺🇸 Atlanta, Georgia, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Georgia Cancer Center at Augusta University; 🇺🇸 Augusta, Georgia, United States

Northeast Georgia Medical Center; 🇺🇸 Gainesville, Georgia, United States

Illinois Cancer Specialists; 🇺🇸 Arlington Heights, Illinois, United States

NorthShore University Health System; 🇺🇸 Evanston, Illinois, United States

St Vincent Hospital; 🇺🇸 Indianapolis, Indiana, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

Our Lady of the Lake Hospital, Inc.; 🇺🇸 Baton Rouge, Louisiana, United States

LSU Health Sciences Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Trials365, LLC; 🇺🇸 Shreveport, Louisiana, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

St. Dominic's Gynecologic Oncology; 🇺🇸 Jackson, Mississippi, United States

Midwest Ventures Group HCA MId America Division; 🇺🇸 Kansas City, Missouri, United States

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States

Women's Cancer Center of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Center Of Hope; 🇺🇸 Reno, Nevada, United States

Women's Cancer Care Associates, LLC; 🇺🇸 Albany, New York, United States

NYU Langone Hospital-Long Island; 🇺🇸 Mineola, New York, United States

Mount Sinai Chelsea; 🇺🇸 New York City, New York, United States

Mount Sinai; 🇺🇸 New York City, New York, United States

Perlmutter Cancer Center at NYU Langone Health; 🇺🇸 New York, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Atrium Health Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Zangmeister Cancer Center; 🇺🇸 Columbus, Ohio, United States

ProMedica Flower Hospital; 🇺🇸 Sylvania, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Oncology Associates of Oregon; 🇺🇸 Eugene, Oregon, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Allegheny Health Network - West Penn Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Magee - Women's Hospital; 🇺🇸 Pittsburg, Pennsylvania, United States

Avera; 🇺🇸 Sioux Falls, South Dakota, United States

Chattanooga's Program in Women's Oncology; 🇺🇸 Chattanooga, Tennessee, United States

The West Clinic, PLLC dba West Cancer Center; 🇺🇸 Germantown, Tennessee, United States

University of Tennessee Medical Center; 🇺🇸 Knoxville, Tennessee, United States

University of Tennessee Health Science Center; 🇺🇸 Memphis, Tennessee, 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

Texas Oncology - Fort Worth; 🇺🇸 Fort Worth, Texas, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States

Texas Oncology - San Antonio; 🇺🇸 San Antonio, Texas, United States

Texas Oncology - The Woodlands; 🇺🇸 The Woodlands, Texas, United States

Texas Oncology, PC, Tyler; 🇺🇸 Tyler, Texas, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, United States

Medical College of Wisconsin/ Freodtert Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

Border Medical Oncology and Haematology; 🇦🇺 Albury East, New South Wales, Australia

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, New South Wales, Australia

Central Coast LHD - Gosford & Wyong Hospitals; 🇦🇺 Gosford, New South Wales, Australia

Newcastle Private Hospital; 🇦🇺 New Lambton Heights, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

Westmead Hospital; 🇦🇺 Wentworthville, New South Wales, Australia

ICON Cancer Centre Southport; 🇦🇺 Southport, Queensland, Australia

Toowoomba Hospital; 🇦🇺 Toowoomba, Queensland, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Box Hill Hospital - Eastern Health (Oncology); 🇦🇺 Box Hill, Victoria, Australia

Monash Health; 🇦🇺 Clayton, Victoria, Australia

Frankston Hospital; 🇦🇺 Frankston, Victoria, Australia

Cabrini Health; 🇦🇺 Malvern, Victoria, Australia

Peter MacCallum Cancer Centre/RWH/RMH; 🇦🇺 Melbourne, Victoria, Australia

The Royal Adelaide Hospital; 🇦🇺 Southport, Australia

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, Belgium

Nova Scotia Health / QEII Health Sciences Centre / Atlantic Clinical Cancer Research Unit; 🇨🇦 Halifax, Nova Scotia, Canada

Princess Margaret; 🇨🇦 Toronto, Ontario, Canada

Sunnybrook Research Institute; 🇨🇦 Toronto, Ontario, Canada

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montreal, Quebec, Canada

McGill University Health Centre (MUHC); 🇨🇦 Montréal, Quebec, Canada

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

High Technology Hospital Medcenter; 🇬🇪 Batumi, Georgia

Tbilisi Cancer Center; 🇬🇪 Tbilisi, Georgia

Caucasus Medical Centre; 🇬🇪 Tbilisi, Georgia

LTD Innova Medical Center; 🇬🇪 Tbilisi, Georgia

Multiprofile Clinic "Consilium Medulla"; 🇬🇪 Tbilisi, Georgia

Charite Berlin Universitatsmedizin; 🇩🇪 Berlin, Germany

KEM | Evang. Kliniken Essen-Mitte, Evang. Huyssens-Stiftung Essen-Huttrop; 🇩🇪 Essen, Germany

Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

University Hospital Dresden; 🇩🇪 Kiel, Germany

Universitatsklinikum Schleswig-Holstein; 🇩🇪 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, Germany

IASO Hospital; 🇬🇷 Maroúsi, Athens, Greece

ALEXANDRA Hospital; 🇬🇷 Athens, Greece

Hygeia Hospital; 🇬🇷 Athens, Greece

Euromedica General Clinic; 🇬🇷 Thessaloníki, Greece

Unit of Gynecol.Oncol., Dept.Obstet.Gynecol., Clinical Center, University of Debrecen; 🇭🇺 Debrecen, Hungary

Petz Aladár University Teaching Hospital; 🇭🇺 Győr, Hungary

Cork University Hospital; 🇮🇪 Cork, Ireland

St. James Hospital; 🇮🇪 Dublin, Ireland

Beacon Hospital Research Institute; 🇮🇪 Dublin, Ireland

Galway University; 🇮🇪 Galway, Ireland

University Hospital Waterford; 🇮🇪 Waterford, Ireland

Hillel-Yaffe Medical Center; 🇮🇱 Hadera, Israel

Wolfson Medical Center; 🇮🇱 Holon, Israel

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

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

Istituto Nazionale dei Tumori IRCCS - MILANO S. C. Ginecologia Oncologica; 🇮🇹 Milano, Italy

Instituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Humanitas San Pio X Hospital; 🇮🇹 Milano, Italy

San Raffaele Hospital; 🇮🇹 Milan, 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

Ospedale Ostetrico Ginecologico Sant'Anna; 🇮🇹 Torino, Italy

AO Ordine Mauriziano; 🇮🇹 Torino, Italy

St. Elisabeth Cancer Institute; 🇸🇰 Bratislava, Slovakia

National Cancer Institute; 🇸🇰 Bratislava, Slovakia

UH Trenčín; 🇸🇰 Trenčín, Slovakia

ICO Badalona; 🇪🇸 Badalona, Spain

Hospital Universitari Vall d' Hebrón; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia Hospitalet; 🇪🇸 Barcelona, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, 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

MD Anderson Cancer Center Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Clinico San Carlos; 🇪🇸 Madrid, Spain

H 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitatrio Virgen de la Victoria; 🇪🇸 Málaga, Spain

Hospital Universitario Virgen del Rocío; 🇪🇸 Sevilla, Spain

Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital LaFe Uacenlia; 🇪🇸 Valencia, Spain

Hospital Clínico Universitario Lozano Blesa; 🇪🇸 Zaragoza, Spain

Hospital Miguel Servet; 🇪🇸 Zaragoza, Spain