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Maintenance With Selinexor/Placebo After Combination Chemotherapy in Participants With Endometrial Cancer [SIENDO] (ENGOT-EN5)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03555422
Recruitment Status : Active, not recruiting
First Posted : June 13, 2018
Last Update Posted : August 15, 2022
Sponsor:
Collaborators:
Belgium and Luxembourg Gynaecological Oncology Group
North-Eastern German Society of Gynaecologic Oncology
Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies
Spanish Research Group in Ovarian Cancer
The Central and Eastern European Gynecologic Oncology Group
Israel Society of Gynecologic Oncology
The GOG Foundation, Inc.
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE May 18, 2018
First Posted Date  ICMJE June 13, 2018
Last Update Posted Date August 15, 2022
Actual Study Start Date  ICMJE January 5, 2018
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2020)
Progression Free Survival (PFS) [ Time Frame: Time from randomization until disease progression (PD) or death, whichever occurs first (approximately 12 months after the last participant enrolled) ]
Compare progression free survival of the two treatment arms as assessed by the investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
Progression Free Survival [ Time Frame: 30 months after FPI ]
Compare progression free survival (PFS) of the two treatment arms
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2020)
  • Progression Free Survival: Assessed by Blinded Independent Central Review (BICR), per RECIST v1.1 [ Time Frame: Time from randomization until PD or death, whichever occurs first (approximately 12 months after the last participant enrolled) ]
    Time from randomization until documented PD or death due to any cause, whichever occurs first. Documented PD will be based on BICR assessments.
  • Disease Specific Survival (DSS) [ Time Frame: Time from randomization until death from endometrial cancer (approximately 12 months after the last participant enrolled) ]
    Time from randomization until date of death from endometrial cancer.
  • Overall Survival (OS) [ Time Frame: Time from randomization until death (approximately 12 months after the last participant enrolled) ]
    Time from randomization until date of death from any cause.
  • Time to First Subsequent Treatment (TFST) [ Time Frame: Time from randomization until first therapy initiation after discontinuation of study drug or death, whichever occurs first (approximately 12 months after the last participant enrolled) ]
    Time from randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first.
  • Progression-free Survival After Subsequent Treatment (PFS2) [ Time Frame: Time from randomization until second documented PD or death (approximately 12 months after the last participant enrolled) ]
    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.
  • Time to Second Subsequent Treatment (TSST) [ Time Frame: Time from randomization until second therapy initiation after discontinuation of study drug or death, whichever occurs first (approximately 12 months after the last participant enrolled) ]
    Time from randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first.
  • Disease Control Rate (DCR) [ Time Frame: Time from randomization up to approximately 16 weeks ]
    Best response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) among patients with PR as best response to prior chemotherapy.
  • Health-Related Quality of Life (HR-QoL): Measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 [ Time Frame: Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled) ]
    Patient-reported outcomes will be measured by the EORTC QLQ C30 questionnaire.
  • Health-Related Quality of Life: Measured by EORTC QLQ-EN24 [ Time Frame: Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled) ]
    Patient-reported outcomes will be measured by the EORTC QLQ-EN24 questionnaire.
  • Health-Related Quality of Life: Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) [ Time Frame: Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled) ]
    Patient-reported outcomes will be measured by the EORTC EQ-5D-5L.
  • Number of Participants with Treatment Emergent Adverse Events (TEAEs), Occurrence, Nature, and Severity of AEs [ Time Frame: From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled) ]
  • Number of Participants with Significant Physical Examination, Clinical Laboratory, and Vital Signs Results [ Time Frame: From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
  • Time to First Subsequent Therapy [ Time Frame: 30 months after FPI ]
    To compare Time to First Subsequent Therapy (TFST) of the two treatment arms
  • PFS after consecutive treatment [ Time Frame: 30 months after FPI ]
    To compare PFS after consecutive treatment (PFS2) of the two treatment arms.. PFS2 is defined along the same timelines as PFS but accounts for the time from randomization to progression or death by any cause on any subsequent line of anticancer therapy
  • Time to Second Subsequent Treatment [ Time Frame: 30 months after FPI ]
    To compare Time to Second Subsequent Treatment (TSST) of the two treatment arms
  • Disease Specific Survival [ Time Frame: 30 months after FPI ]
    To compare Disease Specific Survival (DSS) of the two treatment arms. Disease Specific Survival (DSS) is defined as the time from randomization until date of death from endometrial cancer
  • Overall Survival [ Time Frame: 30 months after FPI ]
    To compare Overall Survival (OS) of the two treatment arms. A patient's overall survival is defined as the time from randomization until date of death from any cause
  • Disease Control Rate [ Time Frame: 30 months after FPI ]
    To compare Disease Control Rate (DCR = Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 12 weeks) of the two treatment arms
  • Health-Related Quality of Life [ Time Frame: 30 months after FPI ]
    To compare Health-Related Quality of Life (HR-QoL) Outcome EORTC QLQ30 of the two treatment arms
  • Health-Related Quality of Life [ Time Frame: 30 months after FPI ]
    To compare Health-Related Quality of Life (HR-QoL) Outcome EORTC-QLQ-EN24 of the two treatment arms
  • Number and percentage of treatment-emergent adverse events as assessed by CTCAE v4.03 [ Time Frame: 30 months after FPI ]
    Assess the safety and tolerability of the two treatment arms by means of AE reports
  • Actual value/changes from baseline for each clinical laboratory parameter relative to CTCAE classification ranges [ Time Frame: 30 months after FPI ]
    Assess the safety and tolerability of the two treatment arms by means of laboratory data
  • Actual value/changes from baseline for vital signs and listing of physical examination findings [ Time Frame: 30 months after FPI ]
    Assess the safety and tolerability of the two treatment arms by means of vital signs and physical examinations
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 31, 2018)
  • Progression free survival [ Time Frame: 30 months after FPI ]
    To compare PFS in the sub-populations of the two treatment arms as described under stratification factors
  • Response Rate [ Time Frame: 30 months after FPI ]
    To compare Response Rate (RR) of the two treatment arms according to RECIST 1.1
  • Duration of Response [ Time Frame: 30 months after FPI ]
    To compare Duration of Response (DOR) of the two treatment arms.
  • Time to progression [ Time Frame: 30 months after FPI ]
    To compare Time to progression (TTP) of the two treatment arms
  • Time Until Definitive Deterioration or Death [ Time Frame: 30 months after FPI ]
    To compare Time Until Definitive Deterioration or Death (TUDD) of the two treatment arms.
  • Prognostic and predictive value of several tumor biomarkers on tumor biopsy /plasma samples as collected at the initial surgery or prior to the start and end of the treatment [ Time Frame: 30 months after FPI ]
    The specific translational research objectives are to evaluate the prognostic and predictive values of tumour biomarkers from tissue / blood samples collected at different timepoints during treatment
  • Evaluation of ctDNA in blood samples collected predose on C1D1 and again on Day one of Cycles 1-X and end of treatment [ Time Frame: 30 months after FPI ]
    The specific translational research objectives are to evaluate the prognostic and predictive values of tumour biomarkers from tissue / blood samples collected at different timepoints during treatment
 
Descriptive Information
Brief Title  ICMJE Maintenance With Selinexor/Placebo After Combination Chemotherapy in Participants With Endometrial Cancer [SIENDO]
Official Title  ICMJE A Randomized, Double-Blind, Phase 3 Trial of Maintenance With Selinexor/ Placebo After Combination Chemotherapy for Patients With Advanced or Recurrent Endometrial Cancer
Brief Summary This is a prospective, multicenter, double-blind, placebo-controlled, randomized Phase 3 study. The purpose of the study is to obtain evidence of efficacy for maintenance selinexor in participants with advanced or recurrent endometrial cancer. Participants 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 in a 2:1 manner to maintenance therapy with 80 milligram (mg) with selinexor once weekly (QW) or placebo until progression.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
double blind placebo controlled study
Primary Purpose: Treatment
Condition  ICMJE Endometrial Cancer
Intervention  ICMJE
  • Drug: Selinexor
    Dose: 80 mg (4 tablets) or 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral
  • Drug: Matching placebo for selinexor
    Dose: 80 mg (4 tablets) or 60 mg (3 tablets); Dosage form: film-coated, immediate-release tablet of 20 mg each; Route of administration: oral
Study Arms  ICMJE
  • Experimental: Selinexor
    Participants will receive fixed dose of selinexor 80 mg (or 60 mg for participants with a body mass index [BMI] less than [<] 20 kilogram per meter square [kg/m^2]) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.
    Intervention: Drug: Selinexor
  • Placebo Comparator: Matching placebo for selinexor
    Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.
    Intervention: Drug: Matching placebo for selinexor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 9, 2020)
248
Original Estimated Enrollment  ICMJE
 (submitted: May 31, 2018)
161
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female, at least 18 years of age at the time of informed consent.
  • Histological confirmed endometrial cancer of the endometrioid, serous, or undifferentiated type. Carcinosarcoma of the uterus is also allowed.
  • Completed a single line of at least 12 weeks of taxane-platinum combination therapy (not including adjuvant or neoadjuvant therapy), and achieved partial remission (PR) or complete remission (CR) according to RECIST version 1.1 for:
  • Primary Stage IV disease, defined as:
  • had a primary or later debulking surgery during first-line taxane-platinum therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks taxane-platinum chemotherapy, OR
  • had a primary or later debulking surgery during first-line taxane-platinum therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease,) and achieved PR or CR after at least 12 weeks taxane-platinum chemotherapy, OR
  • had no surgery and achieved PR or CR after at least 12 weeks taxane-platinum chemotherapy.

OR

  • At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy therapy 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 taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
  • 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 taxane-platinum 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 taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse.

Participants that required their chemotherapy dose held during the 12-week therapy may be considered if they meet the other criteria above and achieve PR or CR per RECIST V1.1.

  • Must be able to initiate study drug 5 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 1.5*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.
  • Hematopoetic function: Absolute neutrophil count (ANC) greater than or equal to (≥) 1.5*10^9/L; platelet count ≥100*10^9 per liter (/L); hemoglobin ≥9.0 gram per deciliter (g/dL).
  • Renal function: estimated creatinine clearance (CrCl) of ≥20 milliliter per minute (mL/min), calculated using the Cockroft Gault formula.
  • In the opinion of the Investigator, the participant must:
  • Have a life expectancy of at least 12 weeks, and
  • Be fit to receive experimental 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 1 week following the last dose of study drug.
  • Written informed consent in accordance with federal, local, and institutional guidelines. The participant must provide informed consent prior to the first Screening procedure.

Exclusion Criteria:

  • Has any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear cell carcinomas.
  • Received a blood or platelet transfusion during 4 weeks prior to randomization.
  • Being treated with a concurrent cancer therapy.
  • Previous treatment with an exportin 1 (XPO1) inhibitor.
  • Previous treatment with anti- programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) immunotherapy (e.g., pembrolizumab).
  • Concurrent treatment with an investigational agent or participation in another clinical trial.
  • Participants 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 cycle 1 day 1 (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).
  • Major injuries or surgery within 14 days prior to C1D1 and/or planned surgery during the on-treatment study period.
  • Previous malignant disease, except participants with other malignant disease, for which the participant 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.
  • Any life-threatening illness, medical condition or organ system dysfunction, which, in the investigator's opinion, could compromise the participant's safety or compliance with the protocol.
  • Known contraindications to selinexor.
  • Known uncontrolled hypersensitivity to the investigational drug, or to its excipients.
  • Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
  • Persistent Grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, with the exception of alopecia.
  • 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).
  • Known unstable cardiovascular function:
  • Symptomatic ischemia, or
  • 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
  • Congestive heart failure of New York Heart Association Class ≥3, or
  • Myocardial infarction within 3 months
  • Females who are pregnant or actively breastfeeding.
  • 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.
  • Active hepatitis C and/or B infection.
  • Participants unable to swallow tablets, participants with malabsorption syndrome, or any other gastrointestinal (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).
  • Psychiatric illness or substance use that would prevent the participant from giving informed consent or being compliant with the study procedures.
  • Participants unwilling or unable to comply with the protocol.
  • Persons who have been committed to an institution by official or judicial order.
  • Participants with dependency on the Sponsor, Investigator or study site.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   China,   Czechia,   Germany,   Greece,   Israel,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03555422
Other Study ID Numbers  ICMJE KCP-330-024
ENGOT-EN5 ( Other Identifier: European Network of Gynaecological Oncological Trial Groups )
BGOG-EN5 ( Other Identifier: Belgium and Luxembourg Gynaecological Oncology Group )
2017-000607-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Karyopharm Therapeutics Inc
Original Responsible Party Universitaire Ziekenhuizen KU Leuven
Current Study Sponsor  ICMJE Karyopharm Therapeutics Inc
Original Study Sponsor  ICMJE Universitaire Ziekenhuizen KU Leuven
Collaborators  ICMJE
  • Belgium and Luxembourg Gynaecological Oncology Group
  • North-Eastern German Society of Gynaecologic Oncology
  • Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies
  • Spanish Research Group in Ovarian Cancer
  • The Central and Eastern European Gynecologic Oncology Group
  • Israel Society of Gynecologic Oncology
  • The GOG Foundation, Inc.
Investigators  ICMJE
Study Director: Michael Kauffman, MD, PhD Karyopharm Therapeutics Inc
PRS Account Karyopharm Therapeutics Inc
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP