Clinical trial NCT03555422: Maintenance with Selinexor/Placebo After Combination Chemotherapy in Participants with 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Endometrial Cancer
Keywords: Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases
Female
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
Collaborators: name: Belgian Gynaecological Oncology Group
name: North-Eastern German Society of Gynaecologic Oncology
name: Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies
name: Spanish Research Group in Ovarian Cancer
name: The Central and Eastern European Gynecologic Oncology Group
name: Israeli Society of Gynecologic Oncology
name: GOG Foundation
First posted: 2018-06-13
Enrollment: 263
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Time from randomization until disease progression (PD) or death, whichever occurs first (approximately 12 months after the last participant enrolled)
Secondary outcomes:
measure: Progression Free Survival: Assessed by Blinded Independent Central Review (BICR), per RECIST v1.1
timeFrame: Time from randomization until PD or death, whichever occurs first (approximately 12 months after the last participant enrolled)
measure: Disease Specific Survival (DSS)
timeFrame: Time from randomization until death from endometrial cancer (approximately 12 months after the last participant enrolled)
measure: Overall Survival (OS)
timeFrame: Time from randomization until death (approximately 12 months after the last participant enrolled)
measure: Time to First Subsequent Treatment (TFST)
timeFrame: 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)
measure: Progression-free Survival After Subsequent Treatment (PFS2)
timeFrame: Time from randomization until second documented PD or death (approximately 12 months after the last participant enrolled)
measure: Time to Second Subsequent Treatment (TSST)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: Time from randomization up to approximately 16 weeks
measure: Health-Related Quality of Life (HR-QoL): Measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
timeFrame: Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled)
measure: Health-Related Quality of Life: Measured by EORTC QLQ-EN24
timeFrame: Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled)
measure: Health-Related Quality of Life: Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
timeFrame: Every 12 weeks during study period, at PD and post PD at 3 and 6 months (approximately 12 months after the last participant enrolled)
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs), Occurrence, Nature, and Severity of AEs
timeFrame: From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled)
measure: Number of Participants with Significant Physical Examination, Clinical Laboratory, and Vital Signs Results
timeFrame: From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists (Sarah Cannon Research Institute)
state: Florida
city: Oak Lawn
country: United States
facility: Gynecological Cancer Institute of Chicago
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: HCA Midwest Health - Kansas City (Sarah Cannon Research Institute)
state: Missouri
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center - Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Nashville
country: United States
facility: Tennessee Oncology Nashville (Sarah Cannon Research Institute)
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology, Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology DFW
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology DFW
state: Texas
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Gent
country: Belgium
facility: UZ Gent
city: Ieper
country: Belgium
facility: Jan Yperman Ziekenhuis
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen K.U. Leuven
city: Namur
country: Belgium
facility: CHU UCL Namur, Site Sainte-Elisabeth
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Verviers
country: Belgium
facility: CHR Verviers
city: London
country: Canada
facility: London Health Sciences Centre (London Regional Cancer Centre)
state: Ontario
city: Toronto
country: Canada
facility: University Health Network (PMCC)
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Maternal and Child Health Hospital
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Shapingba District
city: Wenzhou
country: China
facility: Wenzhou Medical University - The First Affiliated Hospital
state: Zhejiang
city: Brno
country: Czechia
facility: University Hospital Brno
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Prague
country: Czechia
facility: UH Královské Vinohrady
city: Prague
country: Czechia
facility: General University Hospital in Prague
city: Prague
country: Czechia
facility: Hospital Na Bulovce
city: Berlin
country: Germany
facility: Charite Berlin Universitatsmedizin
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Hannover
country: Germany
facility: DIAKOVERE KH gGmbH, Henriettenstift Hannover
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Mainz
country: Germany
facility: Universitätsfrauenklinik Mainz
city: Munich
country: Germany
facility: Klinikum der Universitat Munchen
city: Saarbrücken
country: Germany
facility: Cartitas Klinikum Saarbrücken
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
city: Maroussi
country: Greece
facility: Iaso Hospital
state: Athens
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic
state: Macedonia
city: Athens
country: Greece
facility: ALEXANDRA Hospital
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat -Gan
country: Israel
facility: Sheba Medical Center
city: Candiolo
country: Italy
facility: Istituto di Candiolo, FPO, IRCCS
city: Meldola
country: Italy
facility: Romagnolo Scientific Institute for the Study and Treatment of Tumors
city: Milan
country: Italy
facility: San Raffaele Hospital
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori IRCCS - MILANO S.C. Ginecologia Oncologica
city: Mirano
country: Italy
facility: ULSS 3 SERENISSIMA UOC Oncologia Ed Ematologia Oncologica
city: Naples
country: Italy
facility: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica
city: Rome
country: Italy
facility: Agostino Gemelli University Polyclinic Foundation
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
state: Gipuzkoa
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d' Hebrón
city: Barcelona
country: Spain
facility: Hospital Universitari Clínic de Barcelona
city: Barcelona
country: Spain
facility: Consorci Sanitari de Terrassa
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Sofía
city: Murcia
country: Spain
facility: Virgen de la Arrixaca University Clinical Hospital
city: Palma
country: Spain
facility: Hospital Son Llàtzer
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico de La Fe
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
Study officials:
References: