Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Double blind placebo-controlled study

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: Selinexor
    Dose: 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral
    Other names:
    • KPT-330
Placebo Comparator
Placebo
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
    Dose:60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral

Recruiting Locations

The University of Alabama at Birmingham
Birmingham, Alabama 35205
Contact:
Anna Wilbanks
annaburton@uabmc.edu

Honor Health
Phoenix, Arizona 85016
Contact:
Mei Yu
myu@honorhealth.com

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Mary Blaine
6012786499
mblaine@uams.edu

City of Hope National Medical Center
Duarte, California 91010
Contact:
Hesham Mahmoud
hmahmoud@coh.org

City of Hope at Irvine Lennar
Irvine, California 92618
Contact:
Hesham Mahmoud
hmahmoud@coh.org

UCLA - Women's Health Clinical Research Unit
Los Angeles, California 90095
Contact:
Rachel Gray
310-825-3931
regray@mednet.ucla.edu

Long Beach Memorial Medical Center
Los Angeles, California 90806
Contact:
Laura Macias
LMacias@memorialcare.org

UC Irvine
Orange, California 92868
Contact:
Vanessa Lopez
714-456-3948
vanescl1@hs.uci.edu

Stanford University
Palo Alto, California 94304
Contact:
Bela Shah
650-723-0594
belashah@stanford.edu

California Pacific Medical Center
San Francisco, California 94109
Contact:
Julia Rivera Penafiel
415-600-1102
Julia.riverapenafiel@sutterhealth.org

Broward Health Medical Center
Fort Lauderdale, Florida 33316
Contact:
Toni Rodriquez
9547123949
tsrodriquez@browardhealth.org

Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida 33140
Contact:
Krystal Olivera
305-674-2625
Krystal.Olivera@msmc.com

Emory University
Atlanta, Georgia 30322
Contact:
Nina Kimball
404-778-8145
nina.cathleen.dobbs.kimball@emory.edu

Georgia Cancer Center at Augusta University
Augusta, Georgia 30912
Contact:
Donna Wheatley
17067218978
dwheatley@augusta.edu

Northeast Georgia Medical Center
Gainesville, Georgia 30501
Contact:
Trena Davis
trena.davis@nghs.com

Illinois Cancer Specialists
Arlington Heights, Illinois 60005
Contact:
Laura Lozano
laura.lozano@usoncology.com

NorthShore University Health System
Evanston, Illinois 60201
Contact:
Maria Velez
18475701173
mvelez2@northshore.org

St Vincent Hospital
Indianapolis, Indiana 46260
Contact:
Cynthia Cruz Rivera
317-415-6747
cynthia.cruzrivera@ascension.org

Memorial Hospital of South Bend
South Bend, Indiana 46601
Contact:
Amie Lake
ALake@beaconhealthsystem.org

Our Lady of the Lake Hospital, Inc.
Baton Rouge, Louisiana 70808
Contact:
Tammy Hines
225-924-8394
tammy.hines@fmolhs.org

LSU Health Sciences Center New Orleans
New Orleans, Louisiana 70119
Contact:
Cambri Moeller
cmoel1@lsuhsc.edu

Trials365, LLC
Shreveport, Louisiana 71133
Contact:
Carrie Kay
318-408-1198
c.kay@trials365.org

Tufts Medical Center
Boston, Massachusetts 02111
Contact:
Jill Marshall
617-636-2883
Jill.Marshall@tuftsmedicine.org

Karmanos Cancer Institute
Detroit, Michigan 48201
Contact:
Allison Wolgast
313-576-8994
wolgasta@karmanos.org

St. Dominic's Gynecologic Oncology
Jackson, Mississippi 39216
Contact:
Khadijra Lockwood
601-200-4479
khadijra.lockwood@fmolhs.org

Midwest Ventures Group HCA MId America Division
Kansas City, Missouri 64132
Contact:
Megan Werner
Megan.Werner@hcamidwest.com

Women's Cancer Center of Nevada
Las Vegas, Nevada 89106
Contact:
Jacky Amador
Jamador@wccenter.com

Center Of Hope
Reno, Nevada 89511
Contact:
Shannon Pierpoint
775-327-4673
spierpoint@cohreno.com

Women's Cancer Care Associates, LLC
Albany, New York 12208
Contact:
Nicolina Suriano
518-458-1390
nsuriano@womenscancercareassociates.com

NYU Langone Hospital-Long Island
Mineola, New York 11501
Contact:
Karen Estok
212-404-4434
karen.estok@nyulangone.org

Mount Sinai Chelsea
New York City, New York 10011
Contact:
Neha Kumarley
212-824-7859
neha.kumarley@mssm.edu

Mount Sinai
New York City, New York 10029
Contact:
Neha Kumarley
212-824-7859
neha.kumarley@mssm.edu

Perlmutter Cancer Center at NYU Langone Health
New York, New York 10016
Contact:
Keith Kallas
929-455-2433
keith.kallas@nyulangone.org

Atrium Health Levine Cancer Institute
Charlotte, North Carolina 28209
Contact:
Tesa Adams
Tesa.Adams@atriumhealth.org

Duke Cancer Center
Durham, North Carolina 27710
Contact:
Jennifer Mewshaw
jennifer.mewshaw@duke.edu

University of Cincinnati Medical Center
Cincinnati, Ohio 45219
Contact:
Cara King
513-584-1958
king4cg@ucmail.uc.edu

Zangmeister Cancer Center
Columbus, Ohio 43219
Contact:
Nancy Zangmeister
Nancy.zangmeister@aoncology.com

ProMedica Flower Hospital
Sylvania, Ohio 43560
Contact:
Kendra Mann
Kendra.mann@promedica.org

University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Contact:
Christine Pappaterra
christine-pappaterra@ouhsc.edu

Providence Portland Medical Center
Portland, Oregon 97213
Contact:
Nora Auston
503-215-6427
Nora.Auston@providence.org

Allegheny Health Network - West Penn Hospital
Pittsburgh, Pennsylvania 15224
Contact:
Siobhan Guyach
412-578-4293
siobhan.guyach@ahn.org

Avera
Sioux Falls, South Dakota 57105
Contact:
Teri Kayl
6053221432
teri.kayl@avera.org

Chattanooga's Program in Women's Oncology
Chattanooga, Tennessee 37403
Contact:
Kimberly Donelson
423-266-3636
Kimberly.Donelson@erlanger.org

University of Tennessee Medical Center
Knoxville, Tennessee 37920
Contact:
Krissy Bolig
865-305-7469
klbollig@utmck.edu

Parkland Health & Hospital System
Dallas, Texas 75235
Contact:
Annette Paulsen
Annette.Paulsen@UTSouthwestern.edu

Texas Oncology - Dallas
Dallas, Texas 75246
Contact:
Dominique Marquez
dominique.marquez1@usoncology.com

University of Texas Southwestern Medical Center
Dallas, Texas 75390
Contact:
Annette Paulsen
214-645-9699
annette.paulsen@utsouthwestern.edu

Houston Methodist
Houston, Texas 77030
Contact:
Jaya Kamath
jskamath@houstonmethodist.org

Texas Oncology - San Antonio
San Antonio, Texas 78240
Contact:
Ben Singh
Ben.Singh@mckesson.com

Texas Oncology - The Woodlands
The Woodlands, Texas 77380
Contact:
Taryn Davis
taryn.davis@usoncology.com

Texas Oncology, PC, Tyler
Tyler, Texas 75702
Contact:
Angela Jennings
936-276-0120
Angela.Jennings@McKesson.com

University of Virginia
Charlottesville, Virginia 22908
Contact:
Rachel Lacy
434-243-0126
rmc9p@hscmail.mcc.virginia.edu

University of Wisconsin Hospital and Clinics
Madison, Wisconsin 53792
Contact:
Claire Kostechka
608-263-0796
kostechka@wisc.edu

More Details

NCT ID
NCT05611931
Status
Recruiting
Sponsor
Karyopharm Therapeutics Inc

Study Contact

Karyopharm Medical Information
(888) 209-9326
clinicaltrials@karyopharm.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.