Phase 3 Randomized, Double-Blind Trial of Selinexor Maintenance Versus Placebo Post-Chemotherapy in Advanced or Recurrent Endometrial Cancer
- Trial ID
- 2024-513167-68-00
- Sponsor
- Karyopharm Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is 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**. This objective is clinically relevant as it aims to determine the potential benefit of Selinexor in prolonging disease control and improving patient outcomes in a population with limited treatment options.
Secondary objectives include:
- 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.
- To assess the safety and tolerability of Selinexor.
- 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.
Participants
The clinical trial involves a total of **7 participants** who are exclusively female, aged 18 years and older, diagnosed with **endometrial cancer**. The study population was selected based on specific inclusion criteria, including a histological confirmation of endometrial cancer of the endometrioid, serous, or undifferentiated type, with carcinosarcoma of the uterus also being permissible. Participants must have completed a single line of at least 12 weeks of taxane-platinum combination therapy for Stage IV disease or at first relapse and be in partial or complete remission according to RECIST v1.1. The trial excludes male subjects and does not involve a vulnerable population. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Lifestyle considerations such as diet and physical activity are not specified, but participants must be able to initiate the study drug 5 to 8 weeks after their final dose of chemotherapy. The trial does not provide information on specific lifestyle habits or additional health status details beyond the inclusion criteria.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, Phase 3 study designed to evaluate the efficacy of **Selinexor** as a maintenance therapy compared to placebo in patients with advanced or recurrent **endometrial cancer**. The trial aims to assess the primary endpoint of Progression-Free Survival (PFS), defined as the time from randomization until documented progression of disease (PD) or death from any cause. Secondary endpoints include PFS as assessed by a blinded independent central review, time to first and second subsequent therapies, progression-free survival 2 (PFS2), disease-specific survival, overall survival, and disease-control rate. The trial also evaluates the safety and tolerability of the study treatment through adverse event reports, physical examinations, and clinical laboratory results.
The trial is expected to run from January 1, 2018, to December 31, 2024. Participants will be involved in the study for a maximum treatment period of 4 months, with the possibility of early termination if they experience unacceptable toxicity, disease progression, or withdrawal of consent. The study includes several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age, histological confirmation of endometrial cancer, and completion of prior chemotherapy. Follow-up visits will occur regularly to monitor the patient's response to treatment and any adverse effects. The end-of-study visit will conclude the participant's involvement, assessing the final outcomes and any long-term effects of the treatment.
Treatment
The clinical trial involves the use of **Selinexor**, an experimental medication formulated as a film-coated tablet for **oral use**. The active substance in Selinexor is a chemical compound identified as (2Z)-3-{3-[3,5-bis(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl}-N'-(pyrazin-2-yl)prop-2-enehydrazide. The maximum daily dose of Selinexor is 80 mg, with a total maximum dose of 320 mg over the treatment period. The treatment is administered over a maximum period of 4 weeks. The dosing schedule and participant compliance are monitored throughout the trial to ensure adherence to the protocol.
The study also includes a **placebo** group, where participants receive Selinexor placebo tablets. These tablets are formulated for oral administration and are film-coated, bi-convex, and round in shape. The placebo is used to compare the efficacy of Selinexor as a maintenance therapy in patients with advanced or recurrent **endometrial cancer**. The placebo administration follows the same schedule as the active treatment to maintain the double-blind nature of the trial.
Efficacy
The efficacy of the clinical trial will be assessed primarily through **Progression Free Survival (PFS)**, defined as the time from randomization until documented progression of disease (PD) or death from any cause, whichever occurs first. The primary analysis of PFS will be conducted by the investigator using the RECIST v1.1 criteria. Secondary endpoints include PFS as assessed by a Blinded Independent Central Review (BICR) per RECIST v1.1, time to first subsequent therapy (TFST), time to second subsequent treatment (TSST), progression-free survival 2 (PFS2), disease-specific survival (DSS), and overall survival (OS). Additionally, the disease-control rate (DCR) will be evaluated, defined as the best response of complete response (CR), partial response (PR), or stable disease (SD) for at least 16 weeks.
Patient-reported outcomes will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-EN24. The safety and tolerability of the study treatment will be evaluated based on adverse event (AE) reports, physical examination results, including vital signs, and clinical laboratory results. The occurrence, nature, and severity of AEs will be documented to assess the safety profile of the treatment. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to ensure comprehensive evaluation of the treatment's impact on patients with advanced or recurrent endometrial cancer.
Inclusion and Exclusion 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 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.
- 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.
- 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.
- 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
- 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.
- 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
- 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 XPO1 inhibitor.
- Previous treatment with anti-PD1 or anti-PD-L1 immunotherapy (e.g., pembrolizumab).
- Concurrent treatment with an investigational agent or participation in another clinical trial.
- 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).
- Major injuries or surgery within 14 days prior to C1D1 and/or planned surgery during the on-treatment study period.
- 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.
- 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.
- 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: 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
- 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.
- 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).
- Psychiatric illness or substance use that would prevent the patient from giving informed consent or being compliant with the study procedures.
- Patients unwilling or unable to comply with the protocol.
- Persons who have been committed to an institution by official or judicial order.
- Patients with dependency on the Sponsor, Investigator or study site.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Jan 2018 | 4 |
 Czechia | Not Recruiting | 01 Jan 2018 | 5 |
 Germany | Not Recruiting | 01 Jan 2018 | 7 |
 Greece | Not Recruiting | 01 Jan 2018 | 2 |
 Italy | Not Recruiting | 01 Jan 2018 | 26 |
 Spain | Not Recruiting | 01 Jan 2018 | 26 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
SELINEXOR | Test | — | ORAL USE | 80 | 4 | SUB177942 |
Selinexor placebo for 20 mg tablets is formulated for oral administration. selinexor placebo tablets are film coated bi-convex round tablets | Placebo | N/A | — | — | — | N/A |