Selinexor/placebo will be given as maintenance therapy after combination chemotherapy for patients with advanced endometrial cancer MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: PT Classification code 10014734 Term: Endometrial cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts
Conditions
Sponsors
Karyopharm Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 ß-human chorionic gonadotrop
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: 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.;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.;Timepoint(s) of evaluation of this end point: 12 months after Last Patient In | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;Timepoint(s) of evaluation of this end point: 12 months afer Last Patient Last Visit | — |
Countries
Australia, Belarus, Belgium, Canada, Croatia, Czechia, Czech Republic, Estonia, Germany, Greece, Hungary, Israel, Italy, Lithuania, New Zealand, Poland, Slovakia, Spain, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed