A Study to Evaluate Oral VT-464 in Patients With Castration-Resistant Prostate Cancer

NCT02012920 | Completed Phase 2 FDA Drug

• 2 other identifiers: INO-VT-464-CL-001VMT-VT-464-CL-001
• Study Type: interventional
• Target: 200
• Locations: 4 countries
• Sites: 23

Brief Summary

The goal of this clinical study is to determine the safety, tolerability, pharmacokinetics and activity of Seviteronel, a lyase-selective inhibitor of CYP17, in patients with castration-resistant prostate cancer (CRPC).

Conditions

Castration-resistant Prostate Cancer; CRPC

Keywords

castration-resistant prostate cancer; CYP17; P450c17a; lyase; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Proportion of subjects who have ≥50% PSA decline at any time on study from the start of treatment with seviteronel.

  Review of subjects with defined PSA value decline of greater than or equal to 50% from study start.

  6 months

• 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

  Review of subject disease progression status via CT and measure of median time to progression if progression occurs.

  10 months

Secondary Outcomes (1)

• Radiographic response rate by RECIST 1.1 & PCWG3. Safety of seviteronel with or without concurrent glucocorticoid administration

  10 months

Other Outcomes (1)

• Determine biomarkers for response to seviteronel (e.g., circulating tumor DNA (ctDNA) for AR-v7)

  10 months

Study Arms (2)

Single Failure of Abiraterone or Enzalutamide

EXPERIMENTAL

Seviteronel: given orally once daily in 28 day cycles

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

Double Failure of Abiraterone and Enzalutimide

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

Double Failure of Abiraterone and Enzalutimide; Single Failure of Abiraterone or Enzalutamide

Eligibility Criteria

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

You may qualify if:

• years of age or older 2. Able to provide written informed consent or have their legal representatives provide written informed consent 3. Documented histological or cytological evidence of adenocarcinoma of the prostate. Subjects whose pathology reports are no longer available may be enrolled if, in the opinion of the investigator, the subject has a clinical course consistent with prostatic adenocarcinoma 4. ECOG Performance Status of 0 or 1 5. Undergone orchiectomy, or have ongoing LHRH analogue therapy prior to C1D1. Subjects on LHRH analogues should remain on these agents for the duration of the study 6. Castrate levels of testosterone less than or equal to 50 ng/dl (or 1.7 nmol/L) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values greater than or equal to 1 week between each assessment. The PSA value at the Screening visit must be greater than or equal 2ng/mL with or without: Soft tissue disease progression defined by RECIST 1.1 at Screening or less than or equal to 28 days of C1D1. Measurable disease is not required for entry.
• Lymph nodes greater than or equal to 1.5cm (short axis) are considered measurable disease bone disease progression defined by greater than or equal 2 new lesions on bone scan at Screening, or less than or equal 28 days of C1D1 7. Have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for greater than or equal to 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.
• \. Adequate hematopoietic function as evidenced by:
• WBC greater than or equal to 3,000/μl
• ANC greater than or equal to 1,500/μl
• Platelet count greater than or equal to 100,000/μl
• HGB greater than or equal to 10 g/dl and not transfusion dependent 9. Adequate liver function, including all the following:
• Total serum bilirubin less than or equal to 2.0 x ULN unless the subject has documented Gilbert syndrome;
• Aspartate and alanine aminotransferase (AST \& ALT) less than or equal to 3.0 x ULN or less than or equal to 5.0 x ULN if subject has liver metastasis;
• Alkaline phosphatase less than or equal to 3.0 x ULN or less than or equal to 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 less than or equal to 2.0 mg/dl 11. Potassium (K+) greater than or equal to 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 at Screening and continuing throughout the study period and for 3 months after final study drug administration.
• Two acceptable forms of birth control include:
• Condom (barrier method of contraception), and
• One of the following:
• Oral, injected or implanted hormonal contraception
• Placement of an intrauterine device (IUD) or intrauterine system (ISU)

You may not qualify if:

• Each subject eligible to participate in this study must not have any of the following:
• Received sipuleucel-T (Provenge ®) treatment within 28 days of C1D1
• Received 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 28 days of C1D1
• Received any investigational agent less than or equal to 28 days of C1D1
• Received palliative radiotherapy less than or equal to 2 weeks of C1D1
• Symptomatic CNS metastases
• History of another invasive malignancy less than or equal to 3 years of C1D1
• A QTcF interval of greater than 470 msec; if the Screening ECG QTcF interval is greater than 470 msec, it may be repeated, and if repeat less than or equal to 470 msec, the subject may be enrolled
• 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)
• Started a bone modifying agent (e.g. bisphosphonates, denosumab) less than or equal to 28 days of C1D1 (note: ongoing bone modifying agents administered less than 28 days are allowed)
• Any medical condition that could preclude subject participation in the study, pose an undue medical hazard, or which could interfere with study results
• Class III or IV Congestive Heart Failure (CHF) as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months
• A history of loss of consciousness or transient ischemic attack less than or equal to 12 months of C1D1
• Known active HIV, Hepatitis B, or Hepatitis C infections
• Known or suspected hypersensitivity to seviteronel, or any components of the formulation

Sponsors & Collaborators

• Innocrin Pharmaceutical: lead

Study Sites (23)

Urology Centers of Alabama

Homewood, Alabama, 35209, United States

Location

H. Lee Moffitt Cancer and Research Institute

Tampa, Florida, 33612, United States

Location

First Urology, PSC

Jeffersonville, Indiana, 47130, United States

Location

Wichita Urology

Wichita, Kansas, 67226, United States

Location

Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 86169, United States

Location

North Shore Hematology Oncology Associates

East Setauket, New York, 11733, United States

Location

Associated Medical Professionals of NY

Syracuse, New York, 13210, United States

Location

NY Cancer and Blood Specialists

The Bronx, New York, 10469, United States

Location

Duke Cancer Institute at Cary: Medical Oncology

Cary, North Carolina, 27518, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Urologic Consultants of Southeastern Pennsylvania

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Charleston Hematology Oncology Associates

Charleston, South Carolina, 29414, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Clinics of North Texas

Dallas, Texas, 75231, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Alexandria Hospital, Department of Oncology

Athens, 11528, Greece

Location

Kantonsspital St Gallen, Onkologie/ Hamatologie

Sankt Gallen, Canton of St. Gallen, CH-9007, Switzerland

Location

The Royal Marsden Hospital - Institute of Cancer Research

Sutton, Surrey, United Kingdom

Location

Guys and St. Thomas' NHS Foundation Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 17, 2013
• Study Start: December 1, 2011
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: February 1, 2019

Record last verified: 2019-01

Locations

GR (1); US (19); GB (2); CH (1)