An Investigator-Sponsored Randomized Phase III Trial of Maintenance with Selinexor/ Placebo After Combination Chemotherapy for Patients with Advanced or Recurrent Endometrial Cancer
- Conditions
- advanced endometrial cancerMedDRA version: 20.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10014734Term: Endometrial cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10014736Term: Endometrial cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000607-25-ES
- Lead Sponsor
- ZLEUVEN/BGOG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 161
1.Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
2.Histological confirmed endometrial cancer of the endometrioid, serous, or undifferentiated type. Carcinosarcoma of the uterus is also allowed.
Must have received a paclitaxel-carboplatinum combination in at least one prior therapy.
Prior second-line anthracycline based or again paclitaxel-carboplatin is allowed.
Prior hormonal treatment is allowed.
3. The following patients can be enrolled in the trial:
a)Patients with stage IV disease (FIGO 2009), who have completed first-line taxane-carboplatin combination at least 12 weeks and are in partial or complete remission according to RECIST 1.1, or
b)Patients who have relapsed after primary therapy and have completed paclitaxel -carboplatin combination for at least 12 weeks (4 cycles of 3-or 4 weekly or 12 courses of weekly) for relapse and are in partial or complete remission according to RECIST 1.1, or
c)Patients who have relapsed after primary therapy and have completed a paclitaxel-carboplatin combination and a second-line chemotherapy for at least 12 weeks for relapse and are in partial or complete remission according to RECIST 1.1.
Prior adjuvant for Stage I-III is not counted as a line of chemotherapy unless the relapse occurred within 6 months after the last adjuvant course of chemotherapy for stage I-III disease
4. Patients must be started on study treatment between 3 and 8 weeks after completion of their final dose of the chemotherapy.
5. Patients may have undergone primary surgery. Patients who have had complete cytoreductive surgery (i.e., no visible residual disease) prior to the last chemotherapy are not eligible.
6. Patients may have received vaginal brachytherapy.
7. Patients may have received external beam radiotherapy.
8. Patients may have received hormonal treatment.
9. ECOG performance status of 0-1.
10. Patients must have an adequate organ function.
•Hepatic function: total bilirubin within normal limits; ALT and AST = 2.5 x ULN in pts without liver metastasis. For Pts with liver metastasis: total bilirubin within normal limits, ALT or AST = 2.5 ULN
•Coagulation parameters: International normalised ratio (INR) < 2, prothrombin time (PT) and partial thromboplastin time (PTT) < 50% of deviation of institutional ULN
•Absolute neutrophil count (ANC) = 1.0 x 109/L; platelets = 100 x 109L; haemoglobin = 9.0 g/dL. No blood or platelet transfusion during 4 weeks prior to randomization.Proteinuria < grade 2
•Creatinine < 2,5 ULN or GFR > 30 ml/min (calculated using Cockroft & Gault equation, Jellife equation or measured by EDTA clearance )
•Albumin level > 25 g/l. Intravenous albumin infusion is not allowed during the 2 weeks prior to inclusion.
11. Life expectancy of at least 12 weeks.
12. Patients must be fit to receive experimental therapy.
13. Patient’s age > 18 years.
14. Patients with preserved reproductive capacity must have a negative pregnancy test (ß-HCG test in urine or serum) prior to starting study treatment. Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception). Effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
15. The patient should consent to the sampling of a tumor sample
1. Sarcomas, small cell carcinoma with neuroendocrine differentiation, clear cell carcinomas.
2. Concurrent cancer therapy.
3.Previous treatment with XPO1 Inhibitor.
4.Concurrent treatment with an investigational agent or participation in another clinical trial.
5.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.
6.Major injuries or surgery within the past 14 days prior to start of study treatment
and/or planned surgery during the on-treatment study period.
7.Previous malignant disease, except patients with other malignant disease, for which the patient has been disease-free for at least three years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
8.Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
9.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.
10.Known contraindications to Selinexor.
11.Known uncontrolled hypersensitivity to the investigational drugs, or to their excipients.
12.History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 3 months.
13.History of clinically significant haemorrhage in the past 3 months.
14.Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
15.Persistent grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, except alopecia.
16.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 one month before randomization).
17.Leptomeningeal disease.
18.Unstable cardiovascular function:
•Symptomatic ischemia, or
•Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or
•Congestive heart failure (CHF) of NYHA Class =3, or
•Myocardial infarction (MI) within 3 months
19.Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use 2 medically acceptable methods of contraception for the duration of the trial and for 3 months afterwards.
20.Active or chronic hepatitis C and/or B infection.
21.Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment. 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).
22.Patients unwilling to comply with the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method