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

Recruiting
18 years of age
Both
Phase 3

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Overview

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.

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 (<) 3upper limit of normal (ULN);
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
             to (<=) 2.5ULN 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 (>=) 1.510^9/liter (L); platelet count >= 10010^9/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 details

Endometrial Cancer

NCT05611931

Karyopharm Therapeutics Inc

8 June 2024

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