Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02445976
Recruitment Status : Completed
First Posted : May 15, 2015
Last Update Posted : February 1, 2019
Sponsor:
Collaborators:
Prostate Cancer Foundation
Prostate Cancer Clinical Trials Consortium
Information provided by (Responsible Party):
Innocrin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE May 13, 2015
First Posted Date  ICMJE May 15, 2015
Last Update Posted Date February 1, 2019
Study Start Date  ICMJE May 2015
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
  • Proportion of patients who have a PSA response by while on study from starting treatment with seviteronel [ Time Frame: 6 months ]
    PSA response at any time whilst on study from the start of treatment within seviteronel defined by a ≥ 50% decrease in serum PSA.
  • The time to radiographic disease progression by RECIST 1.1 or PCWG3 [ Time Frame: 10 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 or Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
Original Primary Outcome Measures  ICMJE
 (submitted: May 14, 2015)
The proportion of patients who have a PSA response by 12 weeks of starting treatment with VT-464 [ Time Frame: 12 weeks ]
PSA response to VT-464 within the first 12 weeks of treatment defined by a ≥ 50% decrease in serum PSA.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2015)
  • The proportion of patients who have a PSA response at 12 weeks of starting treatment with VT-464 [ Time Frame: 12 weeks ]
    PSA response to VT-464 at 12 weeks of treatment defined by a ≥ 50% decrease in serum PSA.
  • The median rPFS and 6-month rPFS rate [ Time Frame: 9 months ]
    The rPFS with VT-464 will be evaluated using CT and bone scans.
  • The radiologic response rate [ Time Frame: 9 months ]
    The radiologic response rate with VT-464 will be evaluated using CT and bone scans.
  • The overall response rate [ Time Frame: 36 months ]
    The overall response rate with VT-464 will be evaluated using scheduled follow-up for up to 3 years after discontinuing VT-464.
  • Safety and tolerability assessed by the collection of adverse events will occur from the start of dosing with VT-464 until one month after dosing is discontinued. [ Time Frame: 10 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 14, 2015)
Biomarkers that predict clinical outcomes to VT-464 in CRPC patients who have progressed on enzalutamide or abiraterone. [ Time Frame: 8 months ]
Both circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) from patients will be evaluated to help predict response status to VT-464.
 
Descriptive Information
Brief Title  ICMJE Once-daily Oral Seviteronel in Patients With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone.
Official Title  ICMJE A Phase 2 Open-label Study to Evaluate the Efficacy and Safety of Seviteronel in Subjects With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone
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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Drug: 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
Other Name: Seviteronel
Study Arms  ICMJE
  • Experimental: Prior Abiraterone or Enzalutamide
    Seviteronel: given orally once daily in 28-day cycles
    Intervention: Drug: Seviteronel: given orally once daily in 28-day cycles
  • Experimental: Prior Abiraterone and Enzalutamide
    Seviteronel: given orally once daily in 28-day cycles
    Intervention: Drug: Seviteronel: given orally once daily in 28-day cycles
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: May 26, 2017)
197
Original Estimated Enrollment  ICMJE
 (submitted: May 14, 2015)
148
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02445976
Other Study ID Numbers  ICMJE INO-VT-464-CL-003
VMT-VT-464-CL-003 ( Other Identifier: Innocrin )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Innocrin Pharmaceutical
Study Sponsor  ICMJE Innocrin Pharmaceutical
Collaborators  ICMJE
  • Prostate Cancer Foundation
  • Prostate Cancer Clinical Trials Consortium
Investigators  ICMJE Not Provided
PRS Account Innocrin Pharmaceutical
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP