Clinical Trials Register

Summary
EudraCT Number:	2017-000607-25
Sponsor's Protocol Code Number:	KCP-330-024BGOG-EN5/ENGOT-EN5/SIEND
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-03-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Greece - EOF

A.2

EudraCT number

2017-000607-25

A.3

Full title of the trial

A Randomized, Double-Blind, Phase 3 Trial of Maintenance with Selinexor/ Placebo After Combination Chemotherapy for Patients with Advanced or Recurrent Endometrial Cancer

Τυχαιοποιημένη, Διπλά Τυφλή Μελέτη Φάσης 3 της Συντήρησης με Σελινεξόρη/Εικονικό Φάρμακο
μετά από Συνδυαστική Χημειοθεραπεία σε Ασθενείς με Εξελισσόμενο ή Υποτροπιάζοντα Καρκίνο
του Ενδομητρίου.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Phase 3 Trial of Maintenance with Selinexor/ Placebo After Combination Chemotherapy for Patients with Advanced or Recurrent Endometrial Cancer

A.3.2

Name or abbreviated title of the trial where available

SIENDO/ENGOT-EN5

A.4.1

Sponsor's protocol code number

KCP-330-024BGOG-EN5/ENGOT-EN5/SIEND

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Karyopharm Therapeutics Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Karyopharm Therapeutics Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NEXT CRO
B.5.2	Functional name of contact point	Operational Director
B.5.3	Address:
B.5.3.1	Street Address	G.Souri 15 & Vas. Sofias
B.5.3.2	Town/ city	Marousi
B.5.3.3	Post code	15124
B.5.3.4	Country	Greece
B.5.4	Telephone number	+302106147282
B.5.5	Fax number	+302106141832
B.5.6	E-mail	info@nextcro.eu

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Selinexor
D.3.2	Product code	KPT-330
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Selinexor
D.3.9.2	Current sponsor code	KPT-330
D.3.9.3	Other descriptive name	SELINEXOR
D.3.9.4	EV Substance Code	SUB177942
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Selinexor/placebo will be given as maintenance therapy after combination chemotherapy for patients with advanced endometrial cancer

E.1.1.1

Medical condition in easily understood language

Selinexor/placebo will be given as maintenance therapy after combination chemotherapy for patients with advanced endometrial cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10014733
E.1.2	Term	Endometrial cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10014734
E.1.2	Term	Endometrial cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10014736
E.1.2	Term	Endometrial cancer recurrent
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate and compare the efficacy of selinexor compared to placebo, as assessed by the investigator, as maintenance therapy in patients with advanced or recurrent endometrial cancer.

E.2.2

Secondary objectives of the trial

To evaluate and compare the efficacy of selinexor compared to placebo, as assessed by a blinded independent central review (BICR).
To evaluate and compare selinexor and placebo on survival rates.
To evaluate and compare selinexor and placebo for time to subsequent therapies.
To evaluate and compare selinexor and placebo for efficacy on subsequent therapy.
To evaluate and compare selinexor and placebo for disease control.
To evaluate health-related quality of life (HR-QoL) outcomes.
Assess the safety and tolerability of selinexor.
Exploratory
To evaluate and compare selinexor and placebo on tumor response rate
To evaluate and compare selinexor and placebo on duration of response.
To identify predictive biomarkers of response to treatment and explore treatment mechanism of action using genomics analyses.
To evaluate the pharmacokinetics (PK) of selinexor used as maintenance therapy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Female, at least 18 years of age at the time of informed consent.
2.Histological confirmed endometrial cancer of the endometrioid, serous, or indifferentiated type. Carcinosarcoma of the uterus is also allowed.
3. Completed a single line of at least 12 weeks of taxane-platinum combination therapy (not including adjuvant or neoadjuvant therapy) , and achieved partial or complete remission (PR or CR) according to RECIST version 1.1 for: a. Primary Stage IV disease, d. Defined as:
a.had a primary or later debulking surgery during the first-line taxane-platinum therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved complete response CR after at least 12 weeks taxane-platinum chemotherapy OR b.had a primary or later debulking surgery during first-line the taxane-platinum therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease,) and achieved PR or complete response CR after at least 12 weeks taxane-platinum chemotherapy, OR c.had no surgery and achieved PR or complete response CR after at least 12 weeks taxane-platinum chemotherapy. OR b.At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy therapy for Stage I-IV disease), d. Defined as:
a.had Stage I – III disease at diagnosis and received at initial diagnosis adjuvant chemotherapy and relapsed later. Patients should have PR or complete response CR after at least 12 weeks of taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
b.had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at initial diagnosis and relapsed later. Patients should have PR or complete response CR after at least 12 weeks of taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
c.had Stage IV disease at diagnosis and received initially chemotherapy with or without surgery and relapsed later. At the time of relapse, patients should have PR or complete response CR after at least 12 weeks of taxane-platinum chemotherapy compared with the start of this chemotherapy at the time of relapse.
Patients 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.
4. Must be able to initiate study drug 5 to 8 weeks after completion of their final dose of chemotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Patients must have adequate bone marrow function and organ function within 2 weeks before starting study drug as defined by the following laboratory criteria:
a. Hepatic function: total bilirubin up to 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN in patients without liver metastasis. For patients with known liver involvement of their tumor: AST and ALT ≤5 x ULN.
b. Hematopoetic function: Absolute neutrophil count (ANC) ≥1.5 x 109/L; platelet count ≥100 x 109L; hemoglobin ≥9.0 g/dL.
c. Renal function: estimated creatinine clearance (CrCl) of ≥20 mL/min, calculated using the Cockroft-Gault formula.
7. In the opinion of the Investigator, the patient must:
a. Have a life expectancy of at least 12 weeks, and
b. Be fit to receive experimental therapy
8. 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 patients 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.
9. Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first Screening procedure.

E.4

Principal exclusion criteria

1.Has any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear cell carcinomas.
2.Received a blood or platelet transfusion during 4 weeks prior to randomization.
3.Being treated with a concurrent cancer therapy.
4.Previous treatment with an exportin 1 (XPO1) inhibitor.
5. Previous treatment with anti-PD1 or anti-PD-L1 immunotherapy (e.g., pembrolizumab).
6. Concurrent treatment with an investigational agent or participation in another clinical trial.
7. Patients 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 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).
8. Major injuries or surgery within 14 days prior to C1D1 and/or planned surgery during the on-treatment study period.
9. Previous malignant disease, except patients with other malignant disease, for which the patient 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.
10. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient’s safety or compliance with the protocol.
11. Known contraindications to selinexor.
12. Known uncontrolled hypersensitivity to the investigational drug, or to its excipients.
13. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
14. Persistent Grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, with the exception of alopecia.
15. 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).
16. Known unstable cardiovascular function:
a. Symptomatic ischemia, or
b. 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
c. Congestive heart failure of New York Heart Association Class ≥3, or
d. Myocardial infarction within 3 months
17. Females who are pregnant or actively breastfeeding.
18. 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.
19. Active hepatitis C and/or B infection.
20. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other 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).
21. Psychiatric illness or substance use that would prevent the patient from giving informed consent or being compliant with the study procedures.
22. Patients unwilling or unable to comply with the protocol.
23. Persons who have been committed to an institution by official or judicial order.
24. Patients with dependency on the Sponsor, Investigator or study site.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this study is Progression Free Survival (PFS), which is defined as the time from randomization until documented PD or death due to any cause, whichever occurs first. For the primary analysis of the primary endpoint, documented PD will be determined by the Investigator using RECIST v1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after Last Patient In

E.5.2

Secondary end point(s)

•PFS, as assessed by a BICR, per RECIST v1.1
•Time to first subsequent therapy (TFST) and time to second subsequent treatment (TSST).
•Progression-free survival (PFS2)
•Disease-specific survival (DSS) and overall survival (OS)
•Disease-control rate (DCR; defined as best response of CR, PR, or SD for at least 16 weeks).
•European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire (QLQ)-C30, EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), and EORTC QLQ-EN24.
•The safety and tolerability of study treatment will be evaluated based on AE reports, physical examination results (including vital signs), and clinical laboratory results by means of the occurrence, nature and severity of AEs.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months afer Last Patient Last Visit

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Israel

New Zealand

United States

Estonia

Lithuania

Spain

Czechia

Germany

Italy

Belarus

Belgium

Croatia

Hungary

Slovakia

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of study will be up to 3 years after the last enrolled patient, when
the last patient in the study has withdrawn consent, has been
withdrawn from the study by the Investigator, has died, or has been
lost to follow-up, whichever occurs first

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

170

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

175

F.4.2.2

In the whole clinical trial

248

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the trial, the patients will receive the standard of care follow-up and/or treatment of this condition.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	MITO (Multicenter Italian trials in Ovarian Cancer)
G.4.3.4	Network Country	Italy
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	GEICO (Grupo Español de Investigación de Cáncer de
G.4.3.4	Network Country	Spain
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	NOGGO (North-Eastern-German Society of
G.4.3.4	Network Country	Germany
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	CEEGOG
G.4.3.4	Network Country	Czechia
G.4 Investigator Network to be involved in the Trial: 5
G.4.1	Name of Organisation	UZLEUVEN/BGOG
G.4.3.4	Network Country	Belgium

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-04-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-18

P. End of Trial
P.	End of Trial Status	Ongoing

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