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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karyopharm Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Nov 2017 → 3 Apr 2025

Decision date (initial)

2024-10-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513167-68-00

EudraCT number

2017-000607-25

ClinicalTrials.gov

NCT03555422

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Safety

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.

Secondary objectives 11

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

Conditions and MedDRA coding

endometrial cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Female, at least 18 years of age at the time of informed consent.
2. Histological confirmed endometrial cancer of the endometrioid, serous, or undifferentiated type. Carcinosarcoma of the uterus is also allowed.
3. Completed a single line of at least 12 weeks of taxane-platinum combination therapy for Stage IV disease or at first relapse and is in partial or complete remission according to RECIST v1.1. This includes patients who received taxane-platinum combination therapy for primary Stage IV disease and patients who received taxane-platinum combination therapy for recurrent (i.e., relapse after primary therapy for early stage disease including surgery and/or adjuvant therapy) disease.
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. 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 ≥30 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 must agree to use highly effective methods of contraception throughout the study and for 3 months 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.

Exclusion criteria 24

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 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 7

1. PFS, as assessed by a BICR, per RECIST v1.1
2. Time to first subsequent therapy (TFST) and time to second subsequent treatment (TSST).
3. Progression-free survival (PFS2)
4. Disease-specific survival (DSS) and overall survival (OS)
5. Disease-control rate (DCR; defined as best response of CR, PR, or SD for at least 16 weeks).
6. European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-EN24.
7. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karyopharm Therapeutics Inc.

Sponsor organisation

Karyopharm Therapeutics Inc.

Address

85 Wells Avenue

City

Newton

Postcode

02459-3298

Country

United States

Scientific contact point

Organisation

Karyopharm Therapeutics Inc.

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Karyopharm Therapeutics Inc.

Contact name

Clinical Trial Information Desk

Third parties 4

Locations

6 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications