This is an open-label, Phase 2 clinical study of the oral Selective Inhibitor of Nuclear Export (SINE) selinexor (KPT-330) in patients with metastatic castration-resistant prostate cancer (mCRPC).
This is a Phase 2, open-label study to explore the effect of selinexor (KPT-330) therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Approximately 50 patients are planned for enrollment. Patients will receive an oral dose of selinexor on one of three dosing schedules.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Comparison of different dosages and dosing schedules of drug.
M.D. Anderson Cancer Center
Houston, Texas, United States
Percentage of Participants With Overall Clinical Benefit Response (CBR)
CBR was defined as the point estimate of the percentage of participants who had complete response (CR), partial response (PR), or stable disease (SD) at 12 weeks as per the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1; soft tissue lesions). CR: Disappearance of all target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taken as reference the baseline sum diameter. SD: steady state of disease; non-CR or non-PR or non-progressive disease.
Time frame: At 12 weeks
Progression Free Survival (PFS)
PFS was defined as the time from first dose of study treatment until the disease progression or death due to any cause per RECIST v.1.1 criteria. If date of progression or death occurred after more than 1 missed study visit, participants were censored at the time of last radiologic assessment prior to the missed visit. Participants without documented progression were also censored at the time of last radiologic assessment. Participants without any post baseline assessments were censored at date of start of study therapy.
Time frame: From first dose of study treatment to time of disease progression or death, censored date (up to 23 months)
Percentage of Participants With Best Overall Response: RECIST v1.1 Criteria
Best overall response rate was defined as the percentage of participants who achieved best response of CR, PR as assessed by the RECIST v1.1 criteria. CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taken as reference the baseline sum diameters.
Time frame: From the date of first documented occurrence of response (CR or PR) until the date of documented progression or last disease assessment (up to 23 months)
Absolute Values of Prostate Specific Antigen (PSA) Levels
PSA marker was used for the assessment of disease progression and estimated the PSA level when compared to baseline.
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Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 (each cycle of 28 days) and End of Treatment (30 days after last dose of study treatment)
Percent Change From Baseline in Prostate Specific Antigen Levels
PSA marker was used for the assessment of disease progression and estimated the PSA level when compared to baseline.
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 (each cycle of 28 days) and End of Treatment (30 days after last dose of study treatment)
Prostate Specific Antigen Response Rate
PSA response rate was defined as number of participants who achieved a ≥30% drop in PSA at 12 Weeks when compared to baseline.
Time frame: Baseline up to 12 weeks
Overall Survival (OS)
OS was defined as the time from first dose of study treatment until death due to any cause. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, were censored at the day they were last known to be alive.
Time frame: From first dose of study treatment to death, censored date (up to 23 months)
Pain Intensity Index (PPII) Total Score
Quality of life (QoL) was assessed by verbal rating of participant's pain according to present pain intensity index. Participants were asked to describe "how severe their pain was at very moment". Present pain intensity was assessed on 5-point visual analog scale ranging from 0 to 5, where 0-no pain, 1-mild pain, 2-discomforting pain, 3-distressing pain, 4-horrible pain, and 5-excruciating pain. The higher scores indicated higher pain.
Time frame: Baseline up to 30 days after last dose of study treatment (up to 23 months)
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)
An adverse event (AE) was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. A serious adverse event (SAE) was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, is life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 28 days following last dose or any event considered drug-related by the investigator through the end of the study.
Time frame: From screening up to 23 months