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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03555422

Studienbeginn:
Januar 2018

Letztes Update:
02.02.2021

Wirkstoff:
Selinexor, Matching placebo for selinexor

Indikation (Clinical Trials):
Endometrial Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Karyopharm Therapeutics Inc

Collaborator:
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, CEE

Studienleiter

Michael Kauffman, MD, PhD
Study Director
Karyopharm Therapeutics Inc

Kontakt

Jatin Shah Executive Vice President and Chief Medical Officer, MD
Kontakt:
Phone: (617) 658-0600
E-Mail: jshah@karyopharm.com
» Kontaktdaten anzeigen
Sharon Shacham President and Chief Scientific Officer, PhD
Kontakt:
Phone: (617) 658-0600
E-Mail: sshacham@karyopharm.com
» Kontaktdaten anzeigen

Studienlocations (3 von 67)

Charite Berlin Universitatsmedizin
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Anna-Maria Mira-Conti
Phone: 493 086800 1402
E-Mail: anna-maria.mira-conti@charite.de
» Ansprechpartner anzeigen
DIAKOVERE KH gGmbH, Henriettenstift Hannover
30171 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Willi Pollack
Phone: +49 511 289 3455
E-Mail: willi.pollack@diakovere.de
» Ansprechpartner anzeigen
ViDia Christliche Kliniken Karlsruhe Vincentius-Diakonissen-Kliniken g AG
76137 Karlsruhe
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Lilli Funk
Phone: +49 721 8108 8760
E-Mail: lilli.funk@vincentius-ka.de
» Ansprechpartner anzeigen
Interdisziplinäres Brustzentrum der Universitätsfrauenklinik Ulm
Prittwitzstraße 43
89075 Ulm
(Baden-Württemberg)
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Jessica D'Andrea
Phone: +49 731 500 58521
E-Mail: jessica.dandrea@uniklinik-ulm.de
» Ansprechpartner anzeigen
Florida Cancer Specialists (Sarah Cannon Research Institute)
33401 West Palm Beach
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Colleen Shaw
Phone: 615-524-4016
E-Mail: colleen.shaw@sarahcannon.com
» Ansprechpartner anzeigen
HCA Midwest Health - Kansas City (Sarah Cannon Research Institute)
64132 Kansas City
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Karla McNutt


Phone: 816-276-9698
E-Mail: Karla.McNutt@hcamidwest.com
» Ansprechpartner anzeigen
University of Oklahoma Health Sciences Center - Stephenson Cancer Center
73104 Oklahoma City
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Morgan Hays
Phone: 405-271-8777
Phone (ext.): 48963
E-Mail: Morgan-Hays@ouhsc.edu
» Ansprechpartner anzeigen
Tennessee Oncology Nashville (Sarah Cannon Research Institute)
37203 Nashville
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Colleen Shaw
Phone: 615-524-4016
E-Mail: colleen.shaw@sarahcannon.com
» Ansprechpartner anzeigen
University of Alberta; Cross Cancer Institute
T6G 1Z2 Edmonton
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Usha Kumar
Phone: 780-989-8169
E-Mail: CCISite.Selection@albertahealthservices.ca
» Ansprechpartner anzeigen
London Health Sciences Centre (London Regional Cancer Centre)
N6C 0A7 London
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Patricia Moore
Phone: 519-685-8618
E-Mail: patricia.moore@lhsc.on.ca
» Ansprechpartner anzeigen
McGill University Health Centre (MUHC)
H4A 3J1 Montréal
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Catherine Vigneault
Phone: 514-934-1934
Phone (ext.): 31975
E-Mail: taylor.grant@muhc.mcgill.ca
» Ansprechpartner anzeigen
Romagnolo Scientific Institute for the Study and Treatment of Tumors
47014 Meldola
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Giorgia Ravaglia
Phone: 0039 0543731075
E-Mail: giorgia.ravaglia@irst.emr.it
» Ansprechpartner anzeigen
ULSS 3 SERENISSIMA UOC Oncologia Ed Ematologia Oncologica
Mirano
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Silvia Coccato
Phone: 0039 041 5794433
E-Mail: silvia.coccato@aulss3.veneto.it
» Ansprechpartner anzeigen
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica
80131 Naples
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Margherita Tambaro
Phone: 0039 0815903637
E-Mail: m.tambaro@istitutotumori.na.it
» Ansprechpartner anzeigen
Agostino Gemelli University Polyclinic Foundation
30161 Rome
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Michela Panella
Phone: 0039 063015 8545
E-Mail: michela.panella@policlinicogemelli.it
» Ansprechpartner anzeigen
Hospital Universitari Clínic de Barcelona
08036 Barcelona
SpainRekrutierend» Google-Maps
Ansprechpartner:
Laura Berengue
Phone: +34 93.227.54.00 ext 2811
Phone (ext.): 2811
E-Mail: BERENGUE@clinic.cat
» Ansprechpartner anzeigen
Hospital Universitario Puerta de Hierro - Majadahonda
28220 Madrid
SpainRekrutierend» Google-Maps
Ansprechpartner:
Berenice Brihuega Arribas
Phone: 0034 911917418
E-Mail: bbrihuega@idiphim.org
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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-platinumchemotherapy.

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.

Studien-Rationale

Primary outcome:

1. 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:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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))

12. 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))

Studien-Arme

  • 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.
  • 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.

Geprüfte Regime

  • 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
  • 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

Quelle: ClinicalTrials.gov


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