Maintenance With Selinexor/Placebo After Combination Chemotherapy in Participants With Endometrial Cancer [SIENDO] (ENGOT-EN5)
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| ClinicalTrials.gov Identifier: NCT03555422 |
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Recruitment Status :
Active, not recruiting
First Posted : June 13, 2018
Last Update Posted : December 5, 2023
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Sponsor:
Karyopharm Therapeutics Inc
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
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Endometrial Cancer | Drug: Selinexor Drug: Matching placebo for selinexor | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 263 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 : | December 2024 |
| Estimated Study Completion Date : | December 2024 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Selinexor
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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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.
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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 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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) ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
Criteria
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.
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
Locations
Show 77 study locations
Sponsors and Collaborators
Karyopharm Therapeutics Inc
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.
| Responsible Party: | Karyopharm Therapeutics Inc |
| ClinicalTrials.gov Identifier: | NCT03555422 |
| 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 ) 2017-000607-25 ( EudraCT Number ) |
| First Posted: | June 13, 2018 Key Record Dates |
| Last Update Posted: | December 5, 2023 |
| Last Verified: | December 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Karyopharm Therapeutics Inc:
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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 Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Diseases |