SHIP (Selinexor in Hormone Insensitive Prostate Cancer)

Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Terminated
CT.gov ID
NCT02146833
Collaborator
(none)
20
1
3
23
0.9

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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 Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase-2, Open-Label Study of Oral Selinexor (KPT-330) in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study Start Date :
May 1, 2014
Actual Primary Completion Date :
Apr 1, 2016
Actual Study Completion Date :
Apr 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Selinexor Dosing Regimen 1

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

Drug: Selinexor
Comparison of different dosages and dosing schedules of drug.
Other Names:
  • KPT-330
  • Experimental: Selinexor Dosing Regimen 2

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

    Drug: Selinexor
    Comparison of different dosages and dosing schedules of drug.
    Other Names:
  • KPT-330
  • Experimental: Selinexor Dosing Regimen 3

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

    Drug: Selinexor
    Comparison of different dosages and dosing schedules of drug.
    Other Names:
  • KPT-330
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Overall Clinical Benefit Response (CBR) [At 12 weeks]

      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.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [From first dose of study treatment to time of disease progression or death, censored date (up to 23 months)]

      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.

    2. Percentage of Participants With Best Overall Response: RECIST v1.1 Criteria [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)]

      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.

    3. Absolute Values of Prostate Specific Antigen (PSA) Levels [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)]

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

    4. Percent Change From Baseline in Prostate Specific Antigen Levels [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)]

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

    5. Prostate Specific Antigen Response Rate [Baseline up to 12 weeks]

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

    6. Overall Survival (OS) [From first dose of study treatment to death, censored date (up to 23 months)]

      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.

    7. Pain Intensity Index (PPII) Total Score [Baseline up to 30 days after last dose of study treatment (up to 23 months)]

      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.

    8. Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE) [From screening up to 23 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.

    • Must have received at least one agent known to impact survival (abiraterone, enzalutamide, etc.).

    • Eastern Cooperative Oncology Group (ECOG) less than or equal to (≤ 2) or a Karnofsky Performance Status (KPS) ≥ 60%.

    • Serum testosterone levels less than (<) 50 ng/ml.

    • Ongoing gonadal androgen deprivation therapy with luteinising hormone-releasing hormone (LHRH) analogues or orchiectomy. Participants, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study.

    • Progression of disease despite androgen ablation shown by objective, documented evidence of disease progression (excluding prostate-specific antigen [PSA]), defined as one or both of the following:

    1. Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    2. Bone disease progression defined by modified Prostate Cancer Clinical Trials Working Group 2 (PCWG2) with two or more new lesions or bone scan

    • Discontinuation of all glucocorticoids prescribed to specifically treat prostate cancer (e.g., as a secondary hormonal manipulation) greater than (>) 4 weeks prior to receiving first dose of study drug. Glucocorticoids prescribed for a chronic non-cancer-related illness (e.g., asthma or chronic obstructive pulmonary disease [COPD]) that is well controlled with medical management are permissible to an equivalent of ≤ 10 milligrams (mg) prednisone daily.

    • Laboratory requirements:

    1. White blood cell (WBC) count > 3,000/microliter (μL)

    2. Absolute neutrophil count (ANC) > 1,500/μL

    3. Hemoglobin ≥8.0 gram per deciliter (g/dL)

    4. Platelet count ≥150,000/μL

    5. Serum albumin ≥3.0 g/dL

    6. Calculated or measured creatinine clearance > 30 milliliter per minute (mL/min)

    • A biopsy documenting prostate cancer in a target lesion (e.g., lymph node, bone lesion, or soft tissue lesion) within 3 months prior to study entry.

    • No evidence of chronic or acute disseminated intravascular coagulation or bleeding tendency.

    • Participant must be willing and able to comply with protocol requirements. All participants must sign an informed consent indicating that they are aware of the investigational nature of this study.

    • Participant must be willing and able to sign an authorization for the release of their protected health information for study purposes.

    Exclusion Criteria:
    • Histologic variants other than adenocarcinoma in the primary tumor.

    • Participants who require or may be expected to require urgent treatment with docetaxel during the study (e.g., participants with visceral metastases).

    • Abnormal hepatic function:

    1. Bilirubin > 2 times the upper limit of normal (2 x ULN) (except participants with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must not have a total bilirubin of > 3 x ULN)

    2. Aspartate transaminase (AST) and alanine transaminase (ALT) > 2.5 x ULN (except participants with known liver involvement of their mCRPC who must not have an AST and ALT > 5 x ULN)

    • Therapy with other hormonal therapy, including any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES) within 4 weeks prior to receiving first dose of study drug.

    • Therapy with samarium-153, strontium-89, or radium-223 within 8 weeks prior to first dose of study drug.

    • Uncontrolled infection or concomitant illness that is not controlled with medical management.

    • Prior external beam radiation therapy completed < 3 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.

    • Any "currently active" second malignancy, other than non-melanoma skin cancer. Participants are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months.

    • Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.

    • Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study.

    • Severely compromised immunological state, including known human immunodeficiency virus (HIV).

    • Known acute or chronic hepatitis B or C.

    • Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 3-week washout period before treatment initiation.

    • Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study treatment. Participants receiving ongoing bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to receiving first dose of study treatment. Participants on stable doses of bisphosphonates who show subsequent tumor progression may continue on this medication.

    • Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    1. History or presence of serious uncontrolled ventricular arrhythmias or presence of uncontrolled atrial fibrillation.

    2. Clinically significant resting bradycardia (< 50 beats per minute).

    3. Any of the following within 3 months prior to study entry: myocardial infarction severe/unstable angina, Coronary Artery Bypass Graft, Grade 3 or 4 Congestive Heart Failure, Cerebrovascular Accident, Transient Ischemic Attack, or Pulmonary Embolism.

    4. Uncontrolled hypertension, as defined by a systolic blood pressure > 160 mm Hg and/or a diastolic blood pressure > 90 mm Hg with or without anti-hypertensive medication.

    5. Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring 2 or more interventions per month.

    6. Angina at rest.

    • Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE), version 4.03 Grade of ≤ 1. Chemotherapy induced alopecia or Grade 2 neuropathy is allowed.

    • Any condition or situation, which in the Investigator's opinion, may put the participant at significant risk, confound the study results, or interfere significantly with the participant's participation in the study.

    • Men with a female partner of child-bearing potential, (defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months), who as a couple are unable or unwilling to employ two forms of highly effective contraception (e.g., male condom with spermicide, diaphragm with spermicide, intra-uterine device). Two methods of contraception must be used by participants and their partners through the study and for 3 months after the end of study treatment.

    • Body mass index (BMI) < 1.2 m2, in order to prevent a participant from receiving a dose of selinexor > 70 mg/m2.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 M.D. Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Karyopharm Therapeutics Inc

    Investigators

    • Principal Investigator: Christopher J Logothetis, M.D., M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT02146833
    Other Study ID Numbers:
    • KCP-330-007
    First Posted:
    May 26, 2014
    Last Update Posted:
    Jan 26, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Karyopharm Therapeutics Inc
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at single center in United States of America from May 2014 to 01 April 2016. Due to early termination of study, participants in Arm 2 and 3 were not enrolled.
    Pre-assignment Detail A total of 20 participants were enrolled and treated in the study, of which 9 participants completed the study.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Period Title: Overall Study
    STARTED 20
    COMPLETED 9
    NOT COMPLETED 11

    Baseline Characteristics

    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Overall Participants 20
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    66.3
    (9.62)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    Male
    20
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    5%
    Not Hispanic or Latino
    19
    95%
    Unknown or Not Reported
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    17
    85%
    Black or African American
    1
    5%
    Asian
    1
    5%
    Native Hawaiian or Pacific Islander
    0
    0%
    American Indian or Alaska Native
    0
    0%
    Other
    1
    5%
    Unknown
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Overall Clinical Benefit Response (CBR)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 20
    Number [Percentage of participants]
    25.0
    125%
    2. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Due to early termination, data for this outcome measure was not collected and analyzed.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 0
    3. Secondary Outcome
    Title Percentage of Participants With Best Overall Response: RECIST v1.1 Criteria
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 20
    Number [Percentage of participants]
    0
    0%
    4. Secondary Outcome
    Title Absolute Values of Prostate Specific Antigen (PSA) Levels
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    mITT population was used for this outcome measure. Here, "number analyzed" signifies those participants who were evaluable for each specified time point.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 20
    Baseline
    253.54
    (380.796)
    Cycle 2 Day 1
    1606.42
    (5889.324)
    Cycle 3 Day 1
    204.64
    (316.759)
    Cycle 4 Day 1
    160.50
    (242.479)
    Cycle 5 Day 1
    199.70
    (294.026)
    Cycle 6 Day 1
    253.95
    (388.829)
    Cycle 7 Day 1
    264.40
    (456.858)
    Cycle 8 Day 1
    417.93
    (697.107)
    Cycle 9 Day 1
    17.90
    (24.607)
    Cycle 10 Day 1
    1.30
    (NA)
    Cycle 11 Day 1
    2.00
    (NA)
    End of Treatment
    1026.43
    (2155.744)
    5. Secondary Outcome
    Title Percent Change From Baseline in Prostate Specific Antigen Levels
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    mITT population was used for this outcome measure. Here, "number analyzed" signifies those participants who were evaluable for each specified time point.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 20
    Cycle 2 Day 1
    210.74
    (699.683)
    Cycle 3 Day 1
    80.31
    (90.723)
    Cycle 4 Day 1
    30.51
    (60.739)
    Cycle 5 Day 1
    187.86
    (321.389)
    Cycle 6 Day 1
    281.05
    (457.228)
    Cycle 7 Day 1
    327.46
    (572.347)
    Cycle 8 Day 1
    92.37
    (167.366)
    Cycle 9 Day 1
    1.43
    (84.514)
    Cycle 10 Day 1
    8.33
    (NA)
    Cycle 11 Day 1
    66.67
    (NA)
    End of Treatment
    226.11
    (200.131)
    6. Secondary Outcome
    Title Prostate Specific Antigen Response Rate
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Analysis population included all participants from mITT population who had PSA data at 12 weeks.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 5
    Count of Participants [Participants]
    1
    5%
    7. Secondary Outcome
    Title Overall Survival (OS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Due to early termination, data for this outcome measure was not collected and analyzed.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 0
    8. Secondary Outcome
    Title Pain Intensity Index (PPII) Total Score
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Due to early termination, data for this outcome measure was not collected and analyzed.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 0
    9. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety population: All participants who received any amount of study drug.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    Measure Participants 20
    At least one TEAE
    20
    100%
    At least one TESAE
    9
    45%

    Adverse Events

    Time Frame From screening up to 23 months
    Adverse Event Reporting Description Safety population consisted of all participants who received any amount of study drug.
    Arm/Group Title Arm 1: Selinexor
    Arm/Group Description 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.
    All Cause Mortality
    Arm 1: Selinexor
    Affected / at Risk (%) # Events
    Total 10/20 (50%)
    Serious Adverse Events
    Arm 1: Selinexor
    Affected / at Risk (%) # Events
    Total 9/20 (45%)
    General disorders
    Pain 1/20 (5%)
    Pyrexia 1/20 (5%)
    Infections and infestations
    Influenza 1/20 (5%)
    Pneumonia Parainfluenzae Viral 1/20 (5%)
    Metabolism and nutrition disorders
    Dehydration 1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/20 (5%)
    Myalgia 1/20 (5%)
    Nervous system disorders
    Cerebrovascular Accident 2/20 (10%)
    Hemiparesis 1/20 (5%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism 2/20 (10%)
    Hypoxia 1/20 (5%)
    Other (Not Including Serious) Adverse Events
    Arm 1: Selinexor
    Affected / at Risk (%) # Events
    Total 20/20 (100%)
    Blood and lymphatic system disorders
    Thrombocytopenia 16/20 (80%)
    Anaemia 12/20 (60%)
    Leukopenia 11/20 (55%)
    Lymphopenia 9/20 (45%)
    Neutropenia 5/20 (25%)
    Ear and labyrinth disorders
    Tinnitus 1/20 (5%)
    Endocrine disorders
    Adrenal Insufficiency 1/20 (5%)
    Eye disorders
    Vision Blurred 3/20 (15%)
    Cataract 1/20 (5%)
    Dry Eye 1/20 (5%)
    Photophobia 1/20 (5%)
    Gastrointestinal disorders
    Nausea 11/20 (55%)
    Constipation 7/20 (35%)
    Diarrhoea 5/20 (25%)
    Vomiting 4/20 (20%)
    Anal Incontinence 2/20 (10%)
    Anal Paraesthesia 1/20 (5%)
    Dyspepsia 1/20 (5%)
    Dysphagia 1/20 (5%)
    General disorders
    Fatigue 15/20 (75%)
    Oedema Peripheral 3/20 (15%)
    Gait Disturbance 1/20 (5%)
    Malaise 1/20 (5%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/20 (5%)
    Infections and infestations
    Sinusitis 2/20 (10%)
    Urinary Tract Infection 2/20 (10%)
    Bronchitis 1/20 (5%)
    Upper Respiratory Tract Infection 1/20 (5%)
    Injury, poisoning and procedural complications
    Contusion 1/20 (5%)
    Investigations
    Gamma-Glutamyltransferase Increased 8/20 (40%)
    Aspartate Aminotransferase Increased 7/20 (35%)
    Blood Alkaline Phosphatase Increased 6/20 (30%)
    Alanine Aminotransferase Increased 5/20 (25%)
    Metabolism and nutrition disorders
    Hyperglycaemia 10/20 (50%)
    Abnormal Loss Of Weight 7/20 (35%)
    Decreased Appetite 7/20 (35%)
    Hyponatraemia 6/20 (30%)
    Hypomagnesaemia 5/20 (25%)
    Hypercreatininaemia 4/20 (20%)
    Hypokalaemia 4/20 (20%)
    Hyperkalaemia 3/20 (15%)
    Hyperamylasaemia 2/20 (10%)
    Hypoalbuminaemia 2/20 (10%)
    Hypocalcaemia 2/20 (10%)
    Hypercalcaemia 1/20 (5%)
    Hyperlipasaemia 1/20 (5%)
    Hypophosphataemia 1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/20 (15%)
    Muscular Weakness 3/20 (15%)
    Back pain 2/20 (10%)
    Hypercreatinaemia 2/20 (10%)
    Pain In Extremity 2/20 (10%)
    Bone Pain 1/20 (5%)
    Musculoskeletal Pain 1/20 (5%)
    Myalgia 1/20 (5%)
    Nervous system disorders
    Dizziness 4/20 (20%)
    Dysgeusia 2/20 (10%)
    Hypersomnia 2/20 (10%)
    Amnesia 1/20 (5%)
    Ataxia 1/20 (5%)
    Headache 1/20 (5%)
    Hypoaesthesia 1/20 (5%)
    Somnolence 1/20 (5%)
    Psychiatric disorders
    Insomnia 4/20 (20%)
    Confusional State 3/20 (15%)
    Agitation 1/20 (5%)
    Anxiety 1/20 (5%)
    Personality Change 1/20 (5%)
    Renal and urinary disorders
    Proteinuria 7/20 (35%)
    Haemoglobinuria 2/20 (10%)
    Nocturia 2/20 (10%)
    Urinary Retention 2/20 (10%)
    Haematuria 1/20 (5%)
    Pollakiuria 1/20 (5%)
    Urinary Incontinence 1/20 (5%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 5/20 (25%)
    Pulmonary Embolism 2/20 (10%)
    Cough 1/20 (5%)
    Epistaxis 1/20 (5%)
    Nasal Congestion 1/20 (5%)
    Productive Cough 1/20 (5%)
    Rhinitis Allergic 1/20 (5%)
    Skin and subcutaneous tissue disorders
    Skin Lesion 1/20 (5%)
    Vascular disorders
    Hot Flush 2/20 (10%)
    Deep Vein Thrombosis 1/20 (5%)
    Hypertension 1/20 (5%)
    Hypotension 1/20 (5%)
    Venous Thrombosis 1/20 (5%)

    Limitations/Caveats

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

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jatin Shah, MD
    Organization Karyopharm Therapeutics Inc.
    Phone (617) 658-0600
    Email jshah@karyopharm.com
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT02146833
    Other Study ID Numbers:
    • KCP-330-007
    First Posted:
    May 26, 2014
    Last Update Posted:
    Jan 26, 2021
    Last Verified:
    Jan 1, 2021