SHIP (Selinexor in Hormone Insensitive Prostate Cancer)

NCT02146833 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: KCP-330-007
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Prostate Cancer

Keywords

castrate-resistant prostate cancer; prostate cancer; Karyopharm; KPT-330; selinexor

Outcome Measures

Primary Outcomes (1)

• 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.

  At 12 weeks

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  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

  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

  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

  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

  Baseline up to 12 weeks

Study Arms (3)

Selinexor Dosing Regimen 1

EXPERIMENTAL

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

Drug: Selinexor

Selinexor Dosing Regimen 2

EXPERIMENTAL

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

Drug: Selinexor

Selinexor Dosing Regimen 3

EXPERIMENTAL

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

Drug: Selinexor

Interventions

Selinexor DRUG

Comparison of different dosages and dosing schedules of drug.

Also known as: KPT-330

Selinexor Dosing Regimen 1; Selinexor Dosing Regimen 2; Selinexor Dosing Regimen 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• 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:
• White blood cell (WBC) count \> 3,000/microliter (μL)
• Absolute neutrophil count (ANC) \> 1,500/μL
• Hemoglobin ≥8.0 gram per deciliter (g/dL)
• Platelet count ≥150,000/μL
• Serum albumin ≥3.0 g/dL

You may not qualify if:

• 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:
• 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)
• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (1)

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

selinexor

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc.

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 26, 2014
• Study Start: May 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 26, 2023
• Results First Posted: January 26, 2021

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)