Clinical Trials /

Maintenance With Selinexor/Placebo After Combination Chemotherapy in Endometrial Cancer [SIENDO]

NCT03555422

Description:

Patients with primary stage IV or recurrent disease who are in partial or complete response after having completed a single line of at least 12 weeks of taxane-platinum combo therapy will be randomized to selinexor or placebo until disease progression.

Related Conditions:
  • Endometrial Endometrioid Adenocarcinoma
  • Endometrial Serous Adenocarcinoma
  • Endometrial Undifferentiated Carcinoma
  • Uterine Carcinosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Maintenance With Selinexor/Placebo After Combination Chemotherapy in Endometrial Cancer [SIENDO]
  • Official Title: A Randomized, Double-Blind, Phase 3 Trial of Maintenance With Selinexor/ Placebo After Combination Chemotherapy for Patients With Advanced or Recurrent Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: KCP-330-024
  • SECONDARY ID: ENGOT-EN5
  • SECONDARY ID: BGOG-EN5
  • NCT ID: NCT03555422

Conditions

  • Endometrial Cancer

Interventions

DrugSynonymsArms
SelinexorSelinexor
PlaceboPlacebo

Purpose

Patients with primary stage IV or recurrent disease who are in partial or complete response after having completed a single line of at least 12 weeks of taxane-platinum combo therapy will be randomized to selinexor or placebo until disease progression.

Trial Arms

NameTypeDescriptionInterventions
SelinexorExperimentaloral selinexor 80 mg once weekly 60 mg if BMI <20 kg/m²
  • Selinexor
PlaceboPlacebo Comparatororal placebo once weekly
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Female, at least 18 years of age at the time of informed consent.

          2. Histological confirmed endometrial cancer of the endometrioid, serous, or
             undifferentiated type. Carcinosarcoma of the uterus is also allowed.

          3. Completed a single line of at least 12 weeks of taxane-platinum combination therapy
             for Stage IV disease or at first relapse and is in partial or complete remission
             according to RECIST v1.1. This includes patients who received taxane-platinum
             combination therapy for primary Stage IV disease and patients who received
             taxane-platinum combination therapy for recurrent (i.e., relapse after primary therapy
             for early stage disease including surgery and/or adjuvant therapy) disease.

          4. Must be able to initiate study drug 5 to 8 weeks after completion of their final dose
             of chemotherapy.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          6. Patients must have adequate bone marrow function and organ function within 2 weeks
             before starting study drug as defined by the following laboratory criteria:

               1. Hepatic function: total bilirubin up to 1.5 x upper limit of normal (ULN);
                  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN in
                  patients without liver metastasis. For patients with known liver involvement of
                  their tumor: AST and ALT ≤5 x ULN.

               2. Hematopoetic function: Absolute neutrophil count (ANC) ≥1.5 x 109/L; platelet
                  count ≥100 x 109/L; hemoglobin ≥9.0 g/dL.

               3. Renal function: estimated creatinine clearance (CrCl) of ≥30 mL/min, calculated
                  using the Cockroft Gault formula.

          7. In the opinion of the Investigator, the patient must:

               1. Have a life expectancy of at least 12 weeks, and

               2. Be fit to receive experimental therapy

          8. 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 patients of childbearing potential must agree to use highly effective methods
             of contraception throughout the study and for 3 months following the last dose of
             study drug.

          9. Written informed consent in accordance with federal, local, and institutional
             guidelines. The patient must provide informed consent prior to the first screening
             procedure.

        Exclusion Criteria:

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

          1. Has any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear
             cell carcinomas.

          2. Received a blood or platelet transfusion during 4 weeks prior to randomization.

          3. Being treated with a concurrent cancer therapy.

          4. Previous treatment with an XPO1 inhibitor.

          5. Previous treatment with anti-PD-1 or anti-PD-L1 immunotherapy (e.g., pembrolizumab).

          6. Concurrent treatment with an investigational agent or participation in another
             clinical trial.

          7. Patients who received any systemic anticancer therapy including investigational agents
             or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to
             C1D1. Palliative radiotherapy may be permitted for symptomatic control of pain from
             bone metastases in extremities, provided that the radiotherapy does not involve target
             lesions, and the reason for the radiotherapy does not reflect progressive disease
             (PD).

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

          9. Previous malignant disease, except patients with other malignant disease, for which
             the patient has been disease-free for at least 3 years. Concurrent other malignant
             disease except for curatively treated carcinoma in situ of the cervix or basal cell
             carcinoma of the skin.

         10. Any life-threatening illness, medical condition or organ system dysfunction which, in
             the investigator's opinion, could compromise the patient's safety or compliance with
             the protocol.

         11. Known contraindications to selinexor.

         12. Known uncontrolled hypersensitivity to the investigational drug, or to its excipients.

         13. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.

         14. Persistent Grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, with
             the exception of alopecia.

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

         16. Known unstable cardiovascular function:

               1. Symptomatic ischemia, or

               2. Uncontrolled clinically significant conduction abnormalities (i.e., ventricular
                  tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or
                  asymptomatic left anterior fascicular block /right bundle branch block will not
                  be excluded), or

               3. Congestive heart failure of New York Heart Association Class ≥3, or

               4. Myocardial infarction within 3 months

         17. Females who are pregnant or actively breastfeeding.

         18. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,
             antivirals, or antifungals within 1 week prior to first dose; however, prophylactic
             use of these agents is acceptable even if parenteral.

         19. Active hepatitis C and/or B infection.

         20. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other
             GI disease or GI dysfunction that could interfere with absorption of study drug. A
             history of bowel obstruction requiring a nasogastric tube or intravenous infusion
             during the past 2 months is not allowed (except when this obstruction is caused by
             surgery or other non-malignant causes).

         21. Psychiatric illness or substance use that would prevent the patient from giving
             informed consent or being compliant with the study procedures.

         22. Patients unwilling or unable to comply with the protocol.

         23. Persons who have been committed to an institution by official or judicial order.

         24. Patients with dependency on the Sponsor, Investigator or study site.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:30 months after FPI
Safety Issue:
Description:Compare progression free survival (PFS) of the two treatment arms as assessed by the investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Secondary Outcome Measures

Measure:PFS, as assessed by a Blinded Independent Central Review (BICR), per RECIST v1.1
Time Frame:30 months after FPI
Safety Issue:
Description:Time from randomization until documented Progression of Disease (PD) or death due to any cause, whichever occurs first. Documented PD will be based on BICR assessments.
Measure:Disease specific survival (DSS)
Time Frame:30 months after FPI
Safety Issue:
Description:Time from randomization until date of death from endometrial cancer.
Measure:Overall survival (OS)
Time Frame:30 months after FPI
Safety Issue:
Description:Time from randomization until date of death from any cause.
Measure:Time to first subsequent treatment (TFST)
Time Frame:30 months after FPI
Safety Issue:
Description:Time from randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first.
Measure:Progression-free survival after consecutive treatment (PFS2)
Time Frame:30 months after FPI
Safety Issue:
Description:Time from randomization until the second documented disease progression or death due to any cause by any cause on any subsequent line of anticancer therapy.
Measure:Time to Second Subsequent Treatment (TSST)
Time Frame:30 months after FPI
Safety Issue:
Description:Time from randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first.
Measure:Disease Control Rate (DCR)
Time Frame:30 months after FPI
Safety Issue:
Description:Best response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) among patients with PR as best response to prior chemotherapy.
Measure:Health-Related Quality of Life (HR-QoL) as measured by EORTC QLQ30
Time Frame:30 months after FPI
Safety Issue:
Description:Patient-reported outcomes will be measured by the EORTC QLQ30 questionnaire.
Measure:Health-Related Quality of Life (HR-QoL) as measured by EORTC QLQ-EN24
Time Frame:30 months after FPI
Safety Issue:
Description:Patient-reported outcomes will be measured by the EORTC QLQ-EN24 questionnaire.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Karyopharm Therapeutics Inc

Trial Keywords

  • Endometrial Neoplasms
  • Uterine Neoplasms
  • Genital Neoplasms
  • Neoplasms by Site
  • Neoplasms
  • Uterine Diseases
  • Genital Diseases
  • Female

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