Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma
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
- Endometrial Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- 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
| Arm | Description | Assigned 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. |
|
|
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. |
|
Recruiting Locations
The University of Alabama at Birmingham
Birmingham 4049979, Alabama 4829764 35205
Birmingham 4049979, Alabama 4829764 35205
University of Arkansas for Medical Sciences
Little Rock 4119403, Arkansas 4099753 72205
Little Rock 4119403, Arkansas 4099753 72205
City of Hope National Medical Center
Duarte 5344147, California 5332921 91010
Duarte 5344147, California 5332921 91010
City of Hope at Irvine Lennar
Irvine 5359777, California 5332921 92618
Irvine 5359777, California 5332921 92618
UCLA - Women's Health Clinical Research Unit
Los Angeles 5368361, California 5332921 90095
Los Angeles 5368361, California 5332921 90095
Long Beach Memorial Medical Center
Los Angeles 5368361, California 5332921 90806
Los Angeles 5368361, California 5332921 90806
Stanford University
Palo Alto 5380748, California 5332921 94304
Palo Alto 5380748, California 5332921 94304
California Pacific Medical Center
San Francisco 5391959, California 5332921 94109
San Francisco 5391959, California 5332921 94109
Broward Health Medical Center
Fort Lauderdale 4155966, Florida 4155751 33316
Fort Lauderdale 4155966, Florida 4155751 33316
Mount Sinai Comprehensive Cancer Center
Miami Beach 4164143, Florida 4155751 33140
Miami Beach 4164143, Florida 4155751 33140
Emory University
Atlanta 4180439, Georgia 4197000 30322
Atlanta 4180439, Georgia 4197000 30322
Georgia Cancer Center at Augusta University
Augusta 4180531, Georgia 4197000 30912
Augusta 4180531, Georgia 4197000 30912
Northeast Georgia Medical Center
Gainesville 4196586, Georgia 4197000 30501
Gainesville 4196586, Georgia 4197000 30501
Illinois Cancer Specialists
Arlington Heights 4883555, Illinois 4896861 60005
Arlington Heights 4883555, Illinois 4896861 60005
NorthShore University Health System
Evanston 4891382, Illinois 4896861 60201
Evanston 4891382, Illinois 4896861 60201
St Vincent Hospital
Indianapolis 4259418, Indiana 4921868 46260
Indianapolis 4259418, Indiana 4921868 46260
Memorial Hospital of South Bend
South Bend 4926563, Indiana 4921868 46601
South Bend 4926563, Indiana 4921868 46601
Our Lady of the Lake Hospital, Inc.
Baton Rouge 4315588, Louisiana 4331987 70808
Baton Rouge 4315588, Louisiana 4331987 70808
LSU Health Sciences Center New Orleans
New Orleans 4335045, Louisiana 4331987 70119
New Orleans 4335045, Louisiana 4331987 70119
Trials365, LLC
Shreveport 4341513, Louisiana 4331987 71133
Shreveport 4341513, Louisiana 4331987 71133
Tufts Medical Center
Boston 4930956, Massachusetts 6254926 02111
Boston 4930956, Massachusetts 6254926 02111
Karmanos Cancer Institute
Detroit 4990729, Michigan 5001836 48201
Detroit 4990729, Michigan 5001836 48201
St. Dominic's Gynecologic Oncology
Jackson 4431410, Mississippi 4436296 39216
Jackson 4431410, Mississippi 4436296 39216
Midwest Ventures Group HCA MId America Division
Kansas City 4393217, Missouri 4398678 64132
Kansas City 4393217, Missouri 4398678 64132
Women's Cancer Center of Nevada
Las Vegas 5506956, Nevada 5509151 89106
Las Vegas 5506956, Nevada 5509151 89106
Center Of Hope
Reno 5511077, Nevada 5509151 89511
Reno 5511077, Nevada 5509151 89511
Women's Cancer Care Associates, LLC
Albany 5106834, New York 5128638 12208
Albany 5106834, New York 5128638 12208
NYU Langone Hospital-Long Island
Mineola 5127134, New York 5128638 11501
Mineola 5127134, New York 5128638 11501
Mount Sinai Chelsea
New York 5128581, New York 5128638 10011
New York 5128581, New York 5128638 10011
Perlmutter Cancer Center at NYU Langone Health
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10016
Mount Sinai
New York 5128581, New York 5128638 10029
New York 5128581, New York 5128638 10029
Atrium Health Levine Cancer Institute
Charlotte 4460243, North Carolina 4482348 28209
Charlotte 4460243, North Carolina 4482348 28209
Duke Cancer Center
Durham 4464368, North Carolina 4482348 27710
Durham 4464368, North Carolina 4482348 27710
University of Cincinnati Medical Center
Cincinnati 4508722, Ohio 5165418 45219
Cincinnati 4508722, Ohio 5165418 45219
Zangmeister Cancer Center
Columbus 4509177, Ohio 5165418 43219
Columbus 4509177, Ohio 5165418 43219
ProMedica Flower Hospital
Sylvania 5173572, Ohio 5165418 43560
Sylvania 5173572, Ohio 5165418 43560
University of Oklahoma Health Sciences Center
Oklahoma City 4544349, Oklahoma 4544379 73104
Oklahoma City 4544349, Oklahoma 4544379 73104
Providence Portland Medical Center
Portland 5746545, Oregon 5744337 97213
Portland 5746545, Oregon 5744337 97213
Alliance Cancer Specialists
Langhorne 5197140, Pennsylvania 6254927 19047
Langhorne 5197140, Pennsylvania 6254927 19047
Allegheny Health Network - West Penn Hospital
Pittsburgh 5206379, Pennsylvania 6254927 15224
Pittsburgh 5206379, Pennsylvania 6254927 15224
Avera
Sioux Falls 5231851, South Dakota 5769223 57105
Sioux Falls 5231851, South Dakota 5769223 57105
University of Tennessee Medical Center
Knoxville 4634946, Tennessee 4662168 37920
Knoxville 4634946, Tennessee 4662168 37920
Parkland Health & Hospital System
Dallas 4684888, Texas 4736286 75235
Dallas 4684888, Texas 4736286 75235
Texas Oncology - Dallas
Dallas 4684888, Texas 4736286 75246
Dallas 4684888, Texas 4736286 75246
University of Texas Southwestern Medical Center
Dallas 4684888, Texas 4736286 75390
Dallas 4684888, Texas 4736286 75390
Houston Methodist
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
Texas Oncology - San Antonio
San Antonio 4726206, Texas 4736286 78240
San Antonio 4726206, Texas 4736286 78240
Texas Oncology - The Woodlands
The Woodlands 4736476, Texas 4736286 77380
The Woodlands 4736476, Texas 4736286 77380
Texas Oncology, PC, Tyler
Tyler 4738214, Texas 4736286 75702
Tyler 4738214, Texas 4736286 75702
University of Virginia
Charlottesville 4752031, Virginia 6254928 22908
Charlottesville 4752031, Virginia 6254928 22908
University of Wisconsin Hospital and Clinics
Madison 5261457, Wisconsin 5279468 53792
Madison 5261457, Wisconsin 5279468 53792
More Details
- NCT ID
- NCT05611931
- Status
- Recruiting
- Sponsor
- Karyopharm Therapeutics Inc