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

NCT02445976 | Completed Phase 2

• 2 other identifiers: INO-VT-464-CL-003VMT-VT-464-CL-003
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 21

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

mCRPC; metastatic; castration-resistant prostate cancer

Outcome Measures

Primary Outcomes (2)

• Proportion of patients who have a PSA response by while on study from starting treatment with seviteronel

  PSA response at any time whilst on study from the start of treatment within seviteronel defined by a ≥ 50% decrease in serum PSA.

  6 months

• The time to radiographic disease progression by RECIST 1.1 or PCWG3

  Median time to radiographic disease progression evaluated by computerized tomography (CT scan) or magnetic resonance imaging (MRI) and radionuclide bone scans by RECIST 1.1 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3)

  10 months

Study Arms (2)

Prior Abiraterone or Enzalutamide

EXPERIMENTAL

Seviteronel: given orally once daily in 28-day cycles

Drug: Seviteronel: given orally once daily in 28-day cycles

Prior Abiraterone and Enzalutamide

EXPERIMENTAL

Seviteronel: given orally once daily in 28-day cycles

Drug: Seviteronel: given orally once daily in 28-day cycles

Interventions

Seviteronel: given orally once daily in 28-day cycles DRUG

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

Also known as: Seviteronel

Prior Abiraterone and Enzalutamide; Prior Abiraterone or Enzalutamide

Eligibility Criteria

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

You may qualify if:

• Subjects must be ≥18 years of age.
• Subjects or their legal representatives must be able to provide written informed consent.
• Subjects must have documented histological or cytological evidence of adenocarcinoma of the prostate.
• Subjects must have an ECOG Performance Score of 0-1.
• 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.
• 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
• 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.
• 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
• Subjects must have adequate liver function, including all of the following:

You may not qualify if:

• Subjects who have completed sipuleucel-T (Provenge ®) treatment within 28 days of study drug initiation.
• Subjects on 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 28 days of study drug initiation.
• Subjects who received any investigational agent ≤28 days of study drug initiation.
• Subjects who received palliative radiotherapy ≤2 weeks of study drug initiation.
• Subjects with symptomatic CNS metastases.
• Subjects with a history of another invasive malignancy ≤3 years of study drug initiation.
• 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.
• 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)
• 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).
• 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.
• 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.
• Subject with a history of loss of consciousness or transient ischemic attack ≤ 12 months of study drug initiation.
• Subject with known active HIV, Hepatitis B, or Hepatitis C infections.
• Subject with known or suspected hypersensitivity to seviteronel, or any components of the formulation
• Subject with any other condition which in the opinion of the investigator would preclude participation in the study.

Sponsors & Collaborators

• Innocrin Pharmaceutical: lead
• Prostate Cancer Foundation: collaborator
• Prostate Cancer Clinical Trials Consortium: collaborator

Study Sites (21)

University of Alabama

Birmingham, Alabama, 35249, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85054, United States

Location

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

GU Research Network

Omaha, Nebraska, 68130, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Virginia Oncology Associates

Hampton, Virginia, 23666, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53715, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

seviteronel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 15, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: February 1, 2019

Record last verified: 2019-01

Locations

US (21)