Advanced Gynaecologic Malignancies Cohort A: Ovarian carcinoma Cohort B: Endometrial carcinoma Cohort C: Cervical carcinoma MedDRA version: 20.0 Level: LLT Classification code 10008231 Term: Cervical cancer recurrent System Organ Class: 100000020978 MedDRA version: 20.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10014734 Te
Conditions
Sponsors
Karyopharm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients aged =18 years 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 3. Adequate hematologic function defined as: • platelets = 125 x 109/L • hemoglobin = 5.59 mmol/L or 9 g/dL • ANC = 1.5 x 109/L • WBC = 3.0 x 109/L • Up to 5% deviation is tolerated. Transfusions and growth factors are allowed. 4. Adequate liver function defined as adequate hepatic function within 14 days prior to Cycle 1 Day 1: total bilirubin < 2 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome, who must have a total bilirubin of < 3 times ULN), aspartate aminotransferase (AST) < 2.0 times ULN, and alanine aminotransferase (ALT) < 2.0 times ULN. In the case of known (radiologically and/or biopsy- documented) liver metastasis, AST < 5.0 times ULN and ALT < 5.0 times ULN is acceptable. Up to 10% deviation is acceptable. 5. Renal function defined as a calculated or measured glomerular filtration rate = 30 mL/min. 6. The patient has recovered to Grade = 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of = Grade 2 specified elsewhere in these inclusion criteria. 7. Life expectancy of at least 12 weeks. 8. Able to swallow and retain oral medication. 9. Patients must give informed consent according to the rules and regulations of the individual participating sites. 10.Negative serum pregnancy test in women of childbearing potential within 14 days of first dose of treatment, and patients of childbearing potential must agree to use effective contraception during treatment up to 3 months from last dose. Fertile male partners must be willing and able to use effective non-hormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment. 11.The patient must be recovered from any prior treatment/major operation. The treatment/major operation must be performed at least 4 weeks prior to start of study drug. Palliative radiotherapy is permitted until one week prior to the start of study drug. 12.Only incurable patients with histologically or cytologically proven primary tumor and objective documentation of disease progression on prior treatment by CT/MRI may be enrolled. 13.Ovarian, fallopian tube, or peritoneal carcinoma: both platinum refractory* and platinum resistant** patients, who have received =1 line of chemotherapy for relapsed disease (i.e., = 2 lines of chemotherapy in total). * Platinum refractory is defined as progression during or within 4 weeks of last treatment with a platinum-containing therapy. ** Platinum resistant is defined as relapse 4 weeks to < 6 months after a platinum-containing therapy. 14.Endometrial carcinoma: patients must have received = 1 line of chemotherapy for relapsed or advanced (stage IV, IIIc) disease. 15.Cervical carcinoma: patients must have received = 1 line of chemotherapy for relapsed or advanced (stage IVb) disease. 16.Carcinosarcomas (Malignant Mixed Mullerian Tumor) are allowed, but all other non-epithelial cancers of the ovary, fallopian tube, endometrium, or cervix are excluded. 17.Patients must have either measurable disease per RECIST 1.1 or evaluable disease outside irradiated field on CT/
Exclusion criteria
Exclusion criteria: 1. Disease-Specific Exclusions: • Evidence of complete or partial bowel obstruction. • Need of Total Parenteral Nutrition. 2. Patients who are pregnant or breast feeding. 3. Radiation (except planned or on-going palliative radiation to bone outside of the region of measurable disease) = 3 weeks prior to Cycle 1 Day 1. 4. Chemotherapy, endocrine therapy, immunotherapy or any other systemic anti-cancer therapy (including investigational anti-cancer therapy) = 3 weeks prior to Cycle 1 Day 1. 5. Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated). 6. Unstable cardiovascular function: o Symptomatic ischemia, or o Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on anti-arrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/ RBBB will not be excluded), or o Congestive heart failure (CHF) of NYHA Class = 3, or myocardial infarction (MI) within 3 months of Cycle 1 Day 1. 7. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the patient is clinically stable. 8. Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. 9. Concurrent therapy with approved or investigational anti-cancer therapeutics. 10. Medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. 11. Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and glucocorticoids. 12. All non-epithelial cancers of the ovary, fallopian tube, peritoneum, endometrium or cervix as well as neuro-endocrine tumors are excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of Selinexor in patients with advanced or metastatic gynaecological cancers by disease control rate.;Secondary Objective: • To determine the efficacy of Selinexor in patients with advanced or metastatic gynecological cancers by o Objective response rate (ORR) o Progression-free survival (PFS) o Overall Survival (OS), including OS rates at 12 and 24 months • To evaluate safety and tolerability of Selinexor in patients with advanced or metastatic gynecological cancers. • To evaluate Quality of Life (QoL) for patients with advanced or metastatic gynecological cancers treated with Selinexor • Evaluation of biomarkers in a translational study. • Selinexor PK parameters in a subset of patients.;Primary end point(s): Disease control rate (complete response, partial response + stable disease for at least 12 weeks, assessed according to RECIST 1.1 criteria);Timepoint(s) of evaluation of this end point: After 6 and 12 weeks of treatment and every 8 weeks thereafter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Response to therapy per RECIST 1.1: response for patients in each cohort will be determined by the objective response rate (ORR), defined as either CR or PR using RECIST 1.1 calculated as a proportion and including a two-sided 95% CI for that cohort. 2. Response to therapy per GCIG response criteria (RECIST 1.1 and CA- 125): response for patients in the ovarian cohort will also be assessed for DCR and ORR, as described above, using the GCIG response criteria. 3. Median Progression-free Survival (PFS): PFS for patients in each cohort will be calculated from the date of start of study therapy to the date of PD based on RECIST 1.1, or date of death if PD does not occur. 4. Overall Survival (OS): OS for patients in each cohort will be calculated from the date of start of study therapy to the date of death due to any cause. OS rate at 12 and 24 months will also be calculated. 5. Safety and tolerability of selinexor will be evaluated descriptively for all study patients combined, according to NCI CTCAE, v.4.03. Safety endpoints include AEs, clinical laboratory data, vital signs, ECGs, and physical examinations, further described below. 6. Quality of Life (QoL) will be evaluated for patients in each cohort, and for all study patients combined by EORTC QLQ-C30. 7) Evaluation of biomarkers in a translational study. 8) Pharmacokinetics in a subset of patients;Timepoint(s) of evaluation of this end point: 1) - 3) After 6 and 12 weeks of treatment and every 8 weeks thereafter 4) throughout the trial and every 3 months in FU 5) Throughout the treatment phase until 30 days after last dose 6) After 6 and 12 weeks of treatment and every 8 weeks thereafter as well as End of treatment 7) Baseline and Day 1 in cycles 1-2 8) Cycle 1 day 15 | — |
Countries
Belgium, Denmark
Contacts
Public ContactClinical Trials Information
KaryopharmTherapeutics, Inc.
Outcome results
None listed