Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Hormones

80 mg twice weekly for 4 weeks (8 doses per 28-day cycle)

80 mg once weekly for 4 weeks (4 doses per 28-day cycle)

60 mg twice weekly for 2 weeks, then 1 week off (4 doses per 21-day cycle)

Comparison of different dosages and dosing schedules of drug.

Selinexor

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.

SHIP (Selinexor in Hormone Insensitive Prostate Cancer)

A Phase-2, Open-Label Study of Oral Selinexor (KPT-330) in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

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.

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.

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.

PSA marker was used for the assessment of disease progression and estimated the PSA level when compared to baseline.

PSA response rate was defined as number of participants who achieved a ≥30% drop in PSA at 12 Weeks when compared to baseline.

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.

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.

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.

Karyopharm Therapeutics Inc

Safety population consisted of all participants who received any amount of study drug.

Participants received a dose of 80 mg selinexor twice weekly orally on Days 1, 3, 8, 10, 15, 17, 22, and 24 of 28-day cycle until study discontinuation due to any reason.

Arm 1: Selinexor

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

Safety population included all participants who received any amount of study drug.

This study was terminated due to enrollment challenges. The termination was not a consequence of any safety concern.

Jatin Shah, MD

Modified intent-to-treat (mITT) population:Participants who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment. Participants who received at least 1 dose of study drug, but discontinued treatment prior to first efficacy follow-up assessment due to death, toxicity, or disease progression were also included.

Percentage of Participants With Overall Clinical Benefit Response (CBR)

Due to early termination, data for this outcome measure was not collected and analyzed.

Progression Free Survival (PFS)

mITT population: Participants who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment. In addition participants who received at least 1 dose of study drug, but discontinued treatment prior to first efficacy follow-up assessment due to death, toxicity, or disease progression were also included.

Percentage of Participants With Best Overall Response: RECIST v1.1 Criteria

Baseline

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

Cycle 5 Day 1

Cycle 6 Day 1

Cycle 7 Day 1

Cycle 8 Day 1

Cycle 9 Day 1

Cycle 10 Day 1

Cycle 11 Day 1

End of Treatment

mITT population was used for this outcome measure. Here, "number analyzed" signifies those participants who were evaluable for each specified time point.

Absolute Values of Prostate Specific Antigen (PSA) Levels

Percent Change From Baseline in Prostate Specific Antigen Levels

Analysis population included all participants from mITT population who had PSA data at 12 weeks.

Prostate Specific Antigen Response Rate

Overall Survival (OS)

Pain Intensity Index (PPII) Total Score

At least one TEAE

At least one TESAE

Safety population: All participants who received any amount of study drug.

Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)

Participants received a dose of 80 milligrams (mg) selinexor twice weekly orally on Days 1, 3, 8, 10, 15, 17, 22, and 24 of 28-day cycle until study discontinuation due to any reason.

Spots Global Cancer Trial Database for SHIP (Selinexor in Hormone Insensitive Prostate Cancer)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial