SHIP (Selinexor in Hormone Insensitive Prostate Cancer) (SHIP)

• ClinicalTrials.gov Identifier: NCT02146833
• Recruitment Status: Terminated
• First Posted: May 26, 2014
• Results First Posted: January 26, 2021
• Last Update Posted: January 26, 2023
• Sponsor: Karyopharm Therapeutics Inc
• Information provided by (Responsible Party): Karyopharm Therapeutics Inc

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer
• Intervention: Drug: Selinexor
• Enrollment: 20

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 Details	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
Reason Not Completed
Death	10
No longer consented to study treatment	1

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 Number of Baseline Participants		20
Baseline Analysis Population Description		Safety population included all participants who received any amount of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	20 participants
		66.3 (9.62)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants
	Female	0 0.0%
	Male	20 100.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants
	Hispanic or Latino	1 5.0%
	Not Hispanic or Latino	19 95.0%
	Unknown or Not Reported	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	20 participants
	White	17 85.0%
	Black or African American	1 5.0%
	Asian	1 5.0%
	Native Hawaiian or Pacific Islander	0 0.0%
	American Indian or Alaska Native	0 0.0%
	Other	1 5.0%
	Unknown	0 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.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: Percentage of participants
	25.0

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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

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.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: Percentage of participants
	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.
Overall Number of Participants Analyzed		20
Mean (Standard Deviation); Unit of Measure: Microgram per liter (mcg/L)
Baseline	Number Analyzed	20 participants
		253.54 (380.796)
Cycle 2 Day 1	Number Analyzed	17 participants
		1606.42 (5889.324)
Cycle 3 Day 1	Number Analyzed	10 participants
		204.64 (316.759)
Cycle 4 Day 1	Number Analyzed	6 participants
		160.50 (242.479)
Cycle 5 Day 1	Number Analyzed	6 participants
		199.70 (294.026)
Cycle 6 Day 1	Number Analyzed	6 participants
		253.95 (388.829)
Cycle 7 Day 1	Number Analyzed	4 participants
		264.40 (456.858)
Cycle 8 Day 1	Number Analyzed	3 participants
		417.93 (697.107)
Cycle 9 Day 1	Number Analyzed	2 participants
		17.90 (24.607)
Cycle 10 Day 1	Number Analyzed	1 participants
		1.30 [1] (NA)
Cycle 11 Day 1	Number Analyzed	1 participants
		2.00 [1] (NA)
End of Treatment	Number Analyzed	14 participants
		1026.43 (2155.744)

[1]

Standard deviation was not calculated due to single participant.

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.
Overall Number of Participants Analyzed		20
Mean (Standard Deviation); Unit of Measure: percent change of PSA levels
Cycle 2 Day 1	Number Analyzed	17 participants
		210.74 (699.683)
Cycle 3 Day 1	Number Analyzed	10 participants
		80.31 (90.723)
Cycle 4 Day 1	Number Analyzed	6 participants
		30.51 (60.739)
Cycle 5 Day 1	Number Analyzed	6 participants
		187.86 (321.389)
Cycle 6 Day 1	Number Analyzed	6 participants
		281.05 (457.228)
Cycle 7 Day 1	Number Analyzed	4 participants
		327.46 (572.347)
Cycle 8 Day 1	Number Analyzed	3 participants
		92.37 (167.366)
Cycle 9 Day 1	Number Analyzed	2 participants
		1.43 (84.514)
Cycle 10 Day 1	Number Analyzed	1 participants
		8.33 [1] (NA)
Cycle 11 Day 1	Number Analyzed	1 participants
		66.67 [1] (NA)
End of Treatment	Number Analyzed	14 participants
		226.11 (200.131)

[1]

Standard deviation was not calculated due to single participant.

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.
Overall Number of Participants Analyzed	5
Measure Type: Count of Participants; Unit of Measure: Participants
	1 20.0%

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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

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.
Overall Number of Participants Analyzed	20
Measure Type: Count of Participants; Unit of Measure: Participants
At least one TEAE	20 100.0%
At least one TESAE	9 45.0%

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 (%)
Total	10/20 (50.00%)
Serious Adverse Events
	Arm 1: Selinexor
	Affected / at Risk (%)
Total	9/20 (45.00%)
General disorders
Pain † 1	1/20 (5.00%)
Pyrexia † 1	1/20 (5.00%)
Infections and infestations
Influenza † 1	1/20 (5.00%)
Pneumonia Parainfluenzae Viral † 1	1/20 (5.00%)
Metabolism and nutrition disorders
Dehydration † 1	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/20 (5.00%)
Myalgia † 1	1/20 (5.00%)
Nervous system disorders
Cerebrovascular Accident † 1	2/20 (10.00%)
Hemiparesis † 1	1/20 (5.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism † 1	2/20 (10.00%)
Hypoxia † 1	1/20 (5.00%)
1 Term from vocabulary, MedDRA (20.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm 1: Selinexor
	Affected / at Risk (%)
Total	20/20 (100.00%)
Blood and lymphatic system disorders
Thrombocytopenia † 1	16/20 (80.00%)
Anaemia † 1	12/20 (60.00%)
Leukopenia † 1	11/20 (55.00%)
Lymphopenia † 1	9/20 (45.00%)
Neutropenia † 1	5/20 (25.00%)
Ear and labyrinth disorders
Tinnitus † 1	1/20 (5.00%)
Endocrine disorders
Adrenal Insufficiency † 1	1/20 (5.00%)
Eye disorders
Vision Blurred † 1	3/20 (15.00%)
Cataract † 1	1/20 (5.00%)
Dry Eye † 1	1/20 (5.00%)
Photophobia † 1	1/20 (5.00%)
Gastrointestinal disorders
Nausea † 1	11/20 (55.00%)
Constipation † 1	7/20 (35.00%)
Diarrhoea † 1	5/20 (25.00%)
Vomiting † 1	4/20 (20.00%)
Anal Incontinence † 1	2/20 (10.00%)
Anal Paraesthesia † 1	1/20 (5.00%)
Dyspepsia † 1	1/20 (5.00%)
Dysphagia † 1	1/20 (5.00%)
General disorders
Fatigue † 1	15/20 (75.00%)
Oedema Peripheral † 1	3/20 (15.00%)
Gait Disturbance † 1	1/20 (5.00%)
Malaise † 1	1/20 (5.00%)
Hepatobiliary disorders
Hyperbilirubinaemia † 1	1/20 (5.00%)
Infections and infestations
Sinusitis † 1	2/20 (10.00%)
Urinary Tract Infection † 1	2/20 (10.00%)
Bronchitis † 1	1/20 (5.00%)
Upper Respiratory Tract Infection † 1	1/20 (5.00%)
Injury, poisoning and procedural complications
Contusion † 1	1/20 (5.00%)
Investigations
Gamma-Glutamyltransferase Increased † 1	8/20 (40.00%)
Aspartate Aminotransferase Increased † 1	7/20 (35.00%)
Blood Alkaline Phosphatase Increased † 1	6/20 (30.00%)
Alanine Aminotransferase Increased † 1	5/20 (25.00%)
Metabolism and nutrition disorders
Hyperglycaemia † 1	10/20 (50.00%)
Abnormal Loss Of Weight † 1	7/20 (35.00%)
Decreased Appetite † 1	7/20 (35.00%)
Hyponatraemia † 1	6/20 (30.00%)
Hypomagnesaemia † 1	5/20 (25.00%)
Hypercreatininaemia † 1	4/20 (20.00%)
Hypokalaemia † 1	4/20 (20.00%)
Hyperkalaemia † 1	3/20 (15.00%)
Hyperamylasaemia † 1	2/20 (10.00%)
Hypoalbuminaemia † 1	2/20 (10.00%)
Hypocalcaemia † 1	2/20 (10.00%)
Hypercalcaemia † 1	1/20 (5.00%)
Hyperlipasaemia † 1	1/20 (5.00%)
Hypophosphataemia † 1	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/20 (15.00%)
Muscular Weakness † 1	3/20 (15.00%)
Back pain † 1	2/20 (10.00%)
Hypercreatinaemia † 1	2/20 (10.00%)
Pain In Extremity † 1	2/20 (10.00%)
Bone Pain † 1	1/20 (5.00%)
Musculoskeletal Pain † 1	1/20 (5.00%)
Myalgia † 1	1/20 (5.00%)
Nervous system disorders
Dizziness † 1	4/20 (20.00%)
Dysgeusia † 1	2/20 (10.00%)
Hypersomnia † 1	2/20 (10.00%)
Amnesia † 1	1/20 (5.00%)
Ataxia † 1	1/20 (5.00%)
Headache † 1	1/20 (5.00%)
Hypoaesthesia † 1	1/20 (5.00%)
Somnolence † 1	1/20 (5.00%)
Psychiatric disorders
Insomnia † 1	4/20 (20.00%)
Confusional State † 1	3/20 (15.00%)
Agitation † 1	1/20 (5.00%)
Anxiety † 1	1/20 (5.00%)
Personality Change † 1	1/20 (5.00%)
Renal and urinary disorders
Proteinuria † 1	7/20 (35.00%)
Haemoglobinuria † 1	2/20 (10.00%)
Nocturia † 1	2/20 (10.00%)
Urinary Retention † 1	2/20 (10.00%)
Haematuria † 1	1/20 (5.00%)
Pollakiuria † 1	1/20 (5.00%)
Urinary Incontinence † 1	1/20 (5.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	5/20 (25.00%)
Pulmonary Embolism † 1	2/20 (10.00%)
Cough † 1	1/20 (5.00%)
Epistaxis † 1	1/20 (5.00%)
Nasal Congestion † 1	1/20 (5.00%)
Productive Cough † 1	1/20 (5.00%)
Rhinitis Allergic † 1	1/20 (5.00%)
Skin and subcutaneous tissue disorders
Skin Lesion † 1	1/20 (5.00%)
Vascular disorders
Hot Flush † 1	2/20 (10.00%)
Deep Vein Thrombosis † 1	1/20 (5.00%)
Hypertension † 1	1/20 (5.00%)
Hypotension † 1	1/20 (5.00%)
Venous Thrombosis † 1	1/20 (5.00%)
1 Term from vocabulary, MedDRA (20.1); † Indicates events were collected by systematic assessment

Limitations and 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 Submitted: May 13, 2014
• First Posted: May 26, 2014
• Results First Submitted: December 3, 2020
• Results First Posted: January 26, 2021
• Last Update Posted: January 26, 2023