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

Sponsor

Karyopharm Therapeutics Inc (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03555422

Collaborator

Belgium and Luxembourg Gynaecological Oncology Group (Other), North-Eastern German Society of Gynaecologic Oncology (Other), Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (Other), Spanish Research Group in Ovarian Cancer (Other), The Central and Eastern European Gynecologic Oncology Group (Other), Israel Society of Gynecologic Oncology (Other), The GOG Foundation, Inc. (Other)

248

Enrollment

105

Locations

Arms

61.8

Anticipated Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

248 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 :

Jan 5, 2018

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	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
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.	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

Arm

Intervention/Treatment

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.

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

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.

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

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [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 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 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 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 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 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 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 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 [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 [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) [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 [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 [From first drug administration up to 30 days after last dose (approximately 12 months after the last patient enrolled)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

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 1.5upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (≤) 2.5ULN 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 (≥) 1.510^9/L; platelet count ≥10010^9 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology	Tucson	Arizona	United States	85711
2	The Oncology Institute of Hope and Innovation	Corona	California	United States	92882
3	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
4	Stanford University	Palo Alto	California	United States	94304
5	The Oncology Institute of Hope & Innovation	Whittier	California	United States	90602
6	BRCR Medical Center Inc	Plantation	Florida	United States	33322
7	Moffitt Cancer Center	Tampa	Florida	United States	33612
8	Florida Cancer Specialists (Sarah Cannon Research Institute)	West Palm Beach	Florida	United States	33401
9	Northside Hospital	Atlanta	Georgia	United States	30342
10	Augusta University Medical Center	Augusta	Georgia	United States	30912
11	Sudarshan K. Sharma, Ltd	Hinsdale	Illinois	United States	60521
12	Gynecological Cancer Institute of Chicago	Oak Lawn	Illinois	United States	60453
13	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
14	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
15	Covenant HealthCare	Saginaw	Michigan	United States	48604
16	HCA Midwest Health - Kansas City (Sarah Cannon Research Institute)	Kansas City	Missouri	United States	64132
17	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89052
18	Women's Cancer Care Associates, LLC	Albany	New York	United States	12208
19	Montefiore Medical Center	Bronx	New York	United States	10467
20	NYU Langone	New York	New York	United States	10016
21	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
22	University of Cincinnati	Cincinnati	Ohio	United States	45219
23	University of Oklahoma Health Sciences Center - Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
24	Oncology Associates of Oregon	Eugene	Oregon	United States	97401
25	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
26	Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
27	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
28	Tennessee Oncology Nashville (Sarah Cannon Research Institute)	Nashville	Tennessee	United States	37203
29	Texas Oncology, Austin	Austin	Texas	United States	78731
30	Texas Oncology, Dallas	Dallas	Texas	United States	75246
31	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
32	Texas Oncology Forth Worth	Fort Worth	Texas	United States	76104
33	Texas Oncology, San Antonio	San Antonio	Texas	United States	78240
34	Texas Oncology, The Woodlands	The Woodlands	Texas	United States	77380
35	Texas Oncology, Tyler	Tyler	Texas	United States	75702
36	VCU Massey Cancer Center	Richmond	Virginia	United States	23298
37	Institut Jules Bordet	Brussels		Belgium	1000
38	UZ Gent	Gent		Belgium	9000
39	Jan Yperman Ziekenhuis	Ieper		Belgium	8900
40	Universitaire Ziekenhuizen K.U. Leuven	Leuven		Belgium	3000
41	CHU Ambroise Pare	Mons		Belgium	7000
42	CHU UCL Namur, Site Sainte-Elisabeth	Namur		Belgium	5000
43	AZ Turnhout	Turnhout		Belgium	2300
44	CHR Verviers	Verviers		Belgium	4800
45	University of Alberta; Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
46	London Health Sciences Centre (London Regional Cancer Centre)	London	Ontario	Canada	N6C 0A7
47	University Health Network (PMCC)	Toronto	Ontario	Canada	M5G 2M9
48	McGill University Health Centre (MUHC)	Montréal	Quebec	Canada	H4A 3J1
49	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
50	Affiliated Tumor Hospital of Guizhou Medical University	Guiyang	Guizhou	China	550004
51	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150040
52	Henan Cancer Hospital	Zhengzhou	Henan	China
53	Hunan Cancer Hospital	Changsha	Hunan	China
54	Jiangxi Maternal and Child Health Hospital	Nanchang	Jiangxi	China	330006
55	Liaoning Cancer Hospital	Shenyang	Liaoning	China	110042
56	Obstetrics & Gynecology Hospital of Fudan University	Shanghai	Shanghai	China	200090
57	Chongqing University Cancer Hospital	Chongqing	Shapingba District	China	400000
58	Women's Hospital School of Medicine Zhejiang University	Hangzhou	Zhejiang	China	320000
59	Wenzhou Medical University - The First Affiliated Hospital	Wenzhou	Zhejiang	China	325000
60	University Hospital Brno	Brno		Czechia	60200
61	Palacky University Hospital	Olomouc		Czechia	77900
62	University Hospital Ostrava	Ostrava		Czechia	70852
63	UH Královské Vinohrady	Prague		Czechia	10034
64	General University Hospital in Prague	Prague		Czechia	12851
65	Hospital Na Bulovce	Prague		Czechia	18081
66	Charite Berlin Universitatsmedizin	Berlin		Germany	13353
67	University Hospital Dresden	Dresden		Germany	01307
68	DIAKOVERE KH gGmbH, Henriettenstift Hannover	Hannover		Germany	30171
69	ViDia Christliche Kliniken Karlsruhe Vincentius-Diakonissen-Kliniken g AG	Karlsruhe		Germany	76137
70	Universitatsklinikum Schleswig-Holstein	Kiel		Germany	24105
71	Universitätsklinik Leipzig	Leipzig		Germany	04103
72	Universitätsfrauenklinik Mainz	Mainz		Germany	55131
73	Klinikum der Universitat Munchen	Munich		Germany	80337
74	Cartitas Klinikum Saarbrücken	Saarbrücken		Germany	66113
75	Universitätsfrauenklinik Ulm	Ulm		Germany	89070
76	Iaso Hospital	Maroussi	Athens	Greece	151 23
77	Euromedica General Clinic	Thessaloniki	Macedonia	Greece	54645
78	ALEXANDRA Hospital	Athens		Greece	11528
79	General Hospital of Patras Agios Andreas	Patra		Greece	26335
80	Hillel Yaffe Medical Center	Hadera		Israel	38100
81	Wolfson Medical Center	Holon		Israel	58100
82	Shaare Zedek Medical Center	Jerusalem		Israel	9103102
83	Sheba Medical Center	Ramat -Gan		Israel	52621
84	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
85	Istituto di Candiolo, FPO, IRCCS	Candiolo		Italy	10060
86	Romagnolo Scientific Institute for the Study and Treatment of Tumors	Meldola		Italy	47014
87	San Raffaele Hospital	Milan		Italy	20132
88	Istituto Nazionale dei Tumori IRCCS - MILANO S.C. Ginecologia Oncologica	Milan		Italy	20133
89	ULSS 3 SERENISSIMA UOC Oncologia Ed Ematologia Oncologica	Mirano		Italy	30174
90	Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica	Naples		Italy	80131
91	Agostino Gemelli University Polyclinic Foundation	Rome		Italy	30161
92	Hospital Universitario Donostia	San Sebastián	Gipuzkoa	Spain	20014
93	Hospital Universitari Vall d' Hebrón	Barcelona		Spain	08035
94	Hospital Universitari Clínic de Barcelona	Barcelona		Spain	08036
95	Consorci Sanitari de Terrassa	Barcelona		Spain	08227
96	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
97	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid		Spain	28220
98	Hospital Universitario Infanta Sofía	Madrid		Spain	28702
99	Virgen de la Arrixaca University Clinical Hospital	Murcia		Spain	30120
100	Hospital Son Llàtzer	Palma		Spain	071998
101	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
102	Instituto Valenciano de Oncología	Valencia		Spain	46009
103	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
104	Hospital Universitario y Politécnico de La Fe	Valencia		Spain	46026
105	Hospital Clínico Universitario Lozano Blesa	Zaragoza		Spain	50009