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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03555422
Recruitment Status : Recruiting
First Posted : June 13, 2018
Last Update Posted : November 25, 2019
Sponsor:
Collaborators:
BGOG - Belgium and Luxembourg Gynaecological Oncology Group
NOGGO - North-Eastern German Society of Gynaecologic Oncology
MITO - Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies
GEICO - Spanish Research Group in Ovarian Cancer
CEEGOG - Central and Eastern European Gynecologic Oncology Group
ISGO - Israel Society of Gynecologic Oncology
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Selinexor Drug: Placebo Phase 3

Expanded Access : Karyopharm Therapeutics Inc has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double blind placebo controlled study
Primary Purpose: Treatment
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
Actual Study Start Date : January 5, 2018
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: Selinexor
oral selinexor 80 mg once weekly 60 mg if BMI <20 kg/m²
Drug: Selinexor
oral medication

Placebo Comparator: Placebo
oral placebo once weekly
Drug: Placebo
oral medication




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 30 months after FPI ]
    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 :
  1. PFS, as assessed by a Blinded Independent Central Review (BICR), per RECIST v1.1 [ Time Frame: 30 months after FPI ]
    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.

  2. Disease specific survival (DSS) [ Time Frame: 30 months after FPI ]
    Time from randomization until date of death from endometrial cancer.

  3. Overall survival (OS) [ Time Frame: 30 months after FPI ]
    Time from randomization until date of death from any cause.

  4. Time to first subsequent treatment (TFST) [ Time Frame: 30 months after FPI ]
    Time from randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first.

  5. Progression-free survival after consecutive treatment (PFS2) [ Time Frame: 30 months after FPI ]
    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.

  6. Time to Second Subsequent Treatment (TSST) [ Time Frame: 30 months after FPI ]
    Time from randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first.

  7. Disease Control Rate (DCR) [ Time Frame: 30 months after FPI ]
    Best response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) among patients with PR as best response to prior chemotherapy.

  8. Health-Related Quality of Life (HR-QoL) as measured by EORTC QLQ30 [ Time Frame: 30 months after FPI ]
    Patient-reported outcomes will be measured by the EORTC QLQ30 questionnaire.

  9. Health-Related Quality of Life (HR-QoL) as measured by EORTC QLQ-EN24 [ Time Frame: 30 months after FPI ]
    Patient-reported outcomes will be measured by the EORTC QLQ-EN24 questionnaire.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03555422


Contacts
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Contact: Michael Kauffman, MD, PhD (617) 658-0600 mkauffman@karyopharm.com
Contact: Sharon Shacham, PhD, MBA (617) 658-0600 sshacham@karyopharm.com

  Show 38 Study Locations
Sponsors and Collaborators
Karyopharm Therapeutics Inc
BGOG - Belgium and Luxembourg Gynaecological Oncology Group
NOGGO - North-Eastern German Society of Gynaecologic Oncology
MITO - Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies
GEICO - Spanish Research Group in Ovarian Cancer
CEEGOG - Central and Eastern European Gynecologic Oncology Group
ISGO - Israel Society of Gynecologic Oncology
Investigators
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Study Director: Michael Kauffman, MD, PhD Karyopharm Therapeutics Inc

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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT03555422     History of Changes
Other Study ID Numbers: KCP-330-024
ENGOT-EN5 ( Other Identifier: European Network of Gynaecological Oncological Trial Groups )
BGOG-EN5 ( Other Identifier: Belgium and Luxembourg Gynaecological Oncology Group )
First Posted: June 13, 2018    Key Record Dates
Last Update Posted: November 25, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karyopharm Therapeutics Inc:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases
Female
Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female