Once-daily Oral Seviteronel in Patients With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone.

NCT ID: NCT02445976

Last Updated: 2019-02-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-31

Study Completion Date

2019-01-31

Brief Summary

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The goal of this clinical study is to determine the efficacy and safety of Seviteronel, a lyase-selective inhibitor of CYP17 and an androgen receptor antagonist, in patients with castration-resistant prostate cancer (CRPC) who have been previously treated with enzalutamide and/or abiraterone.

Detailed Description

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This is a phase 2 clinical trial of Seviteronel (an oral, potent and lyase-selective CYP17 inhibitor) in men with castration-resistant prostate cancer (CRPC) progressing on enzalutamide or abiraterone. Approximately 197 subjects will be used to assess treatment efficacy. The study will be conducted in two different clinical cohorts separated by prior exposure to enzalutamide or abiraterone, or prior exposure to enzalutamide and abiraterone.

Conditions

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Prostate Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open Label

Study Groups

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Prior Abiraterone or Enzalutamide

Seviteronel: given orally once daily in 28-day cycles

Group Type EXPERIMENTAL

Seviteronel: given orally once daily in 28-day cycles

Intervention Type DRUG

Oral Seviteronel given once daily, in continuous 28-day cycles at the recommended Phase 2 dose

Prior Abiraterone and Enzalutamide

Seviteronel: given orally once daily in 28-day cycles

Group Type EXPERIMENTAL

Seviteronel: given orally once daily in 28-day cycles

Intervention Type DRUG

Oral Seviteronel given once daily, in continuous 28-day cycles at the recommended Phase 2 dose

Interventions

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Seviteronel: given orally once daily in 28-day cycles

Oral Seviteronel given once daily, in continuous 28-day cycles at the recommended Phase 2 dose

Intervention Type DRUG

Other Intervention Names

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Seviteronel

Eligibility Criteria

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Inclusion Criteria

1. Subjects must be ≥18 years of age.
2. Subjects or their legal representatives must be able to provide written informed consent.
3. Subjects must have documented histological or cytological evidence of adenocarcinoma of the prostate.
4. Subjects must have an ECOG Performance Score of 0-1.
5. Subjects must have undergone orchiectomy, or have ongoing LHRH analogue therapy prior to drug initiation. Subjects on LHRH analogues must remain on these agents for the duration of the study.
6. Subjects must have castrate levels of testosterone (≤50 ng/dl \[1.7 nmol/L\]) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values ≥1 week between each assessment. The PSA value at the Screening visit must be ≥2ng/mL with or without:

* Soft tissue disease progression defined by RECIST 1.1 at Screening or ≤ 28 days of C1D1. Measurable disease is not required for entry. Lymph nodes ≥ 1.5cm (short axis) are considered measurable disease (PCWG3)
* Bone disease progression defined by ≥2 new lesions on bone scan at Screening, or ≤28 days of C1D1
7. Subjects must have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for ≥12 weeks. Other second generation CYP17 inhibitors/androgen receptor antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place of enzalutamide.
8. Subjects must have adequate hematopoietic function as evidenced by:

* WBC ≥3,000/µl
* ANC ≥1,500/µl
* Platelet count ≥100,000/µl
* HGB ≥10 g/dl and not transfusion dependent
9. Subjects must have adequate liver function, including all of the following:

* Total serum bilirubin ≤2.0 x ULN unless the subject has documented Gilbert syndrome;
* Aspartate and alanine aminotransferase (AST \& ALT) ≤3.0 x ULN or ≤5.0 x ULN if subject has liver metastasis;
* Alkaline phosphatase ≤2.0 x ULN or ≤5 x ULN in case of bone metastasis and/or hepatic metastasis
10. Subjects must have adequate renal function as evidenced by a serum creatinine of \<2.0 mg/dl.
11. Subjects must have potassium (K+) \>3.5 mEq/l.
12. Subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting a Screening and continuing throughout the study period and for 3 months after final study drug administration • Two acceptable forms of birth control include:

1\. Condom (barrier method of contraception), and 2. One of the following:

1. Oral, injected or implanted hormonal contraception
2. Placement of an intrauterine device (IUD) or intrauterine system (ISU)
3. Additional barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
4. Vasectomy or surgical castration ≥ 6 months prior to Screening. 13. Subjects able to swallow study medication 14. Subjects able to comply with study requirements

Exclusion Criteria

1. Subjects who have completed sipuleucel-T (Provenge ®) treatment within 28 days of study drug initiation.
2. Subjects on 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 28 days of study drug initiation.
3. Subjects who received any investigational agent ≤28 days of study drug initiation.
4. Subjects who received palliative radiotherapy ≤2 weeks of study drug initiation.
5. Subjects with symptomatic CNS metastases.
6. Subjects with a history of another invasive malignancy ≤3 years of study drug initiation.
7. Subjects with a QTcF interval of \>470 msec; if the Screening ECG QTcF interval is \>470 msec, it may be repeated, and if repeat \<470 msec, the subject may be enrolled.
8. Subject with clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place)
9. Subject that started a bone modifying agent (e.g. bisphosphonates, denosumab) ≤ 28 days of study drug initiation (note: ongoing bone modifying agents administered \> 28 days are allowed).
10. Subject with any medical condition that could preclude subject participation in the study, pose an undue medical hazard, or which could interfere with study results.
11. Subject with Class III or IV Congestive Heart Failure as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months.
12. Subject with a history of loss of consciousness or transient ischemic attack ≤ 12 months of study drug initiation.
13. Subject with known active HIV, Hepatitis B, or Hepatitis C infections.
14. Subject with known or suspected hypersensitivity to seviteronel, or any components of the formulation
15. Subject with any other condition which in the opinion of the investigator would preclude participation in the study.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Prostate Cancer Foundation

OTHER

Sponsor Role collaborator

Prostate Cancer Clinical Trials Consortium

OTHER

Sponsor Role collaborator

Innocrin Pharmaceutical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of California at Los Angeles

Los Angeles, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Tulane University

New Orleans, Louisiana, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

GU Research Network

Omaha, Nebraska, United States

Site Status

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Virginia Oncology Associates

Hampton, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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VMT-VT-464-CL-003

Identifier Type: OTHER

Identifier Source: secondary_id

INO-VT-464-CL-003

Identifier Type: -

Identifier Source: org_study_id

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