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Trial record 1 of 1 for:    A Single-Arm, Phase 2 Study to Evaluate the Safety and Efficacy of VT-464 in Patients with Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone
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Once-daily Oral VT-464 in Patients With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone.

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Innocrin Pharmaceutical
Sponsor:
Collaborators:
Prostate Cancer Foundation
Prostate Cancer Clinical Trials Consortium
Information provided by (Responsible Party):
Innocrin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT02445976
First received: May 13, 2015
Last updated: September 2, 2016
Last verified: August 2016
  Purpose
The goal of this clinical study is to determine the safety and efficacy of VT-464, 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 or abiraterone.

Condition Intervention Phase
Prostate Cancer
Drug: VT-464: given orally once daily in 28-day cycles
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-arm, Phase 2 Study to Evaluate the Safety and Efficacy of VT-464 in Patients With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone.

Resource links provided by NLM:


Further study details as provided by Innocrin Pharmaceutical:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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.


Estimated Enrollment: 148
Study Start Date: May 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prior Enzalutamide - Responded
VT-464: given orally once daily in 28-day cycles
Drug: VT-464: given orally once daily in 28-day cycles
Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose
Other Name: VT-464
Experimental: Prior Enzalutamide - No Response
VT-464: given orally once daily in 28-day cycles
Drug: VT-464: given orally once daily in 28-day cycles
Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose
Other Name: VT-464
Experimental: Prior Abiraterone - Responded
VT-464: given orally once daily in 28-day cycles
Drug: VT-464: given orally once daily in 28-day cycles
Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose
Other Name: VT-464
Experimental: Prior Abiraterone - No Response
VT-464: given orally once daily in 28-day cycles
Drug: VT-464: given orally once daily in 28-day cycles
Oral VT-464 given once daily, in continuous 28-day cycles at the recommended Phase 2 dose
Other Name: VT-464

Detailed Description:
This is a phase 2 clinical trial of VT-464 (an oral, potent and lyase-selective CYP17 inhibitor) in chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) progressing on enzalutamide or abiraterone. A maximal 148 patient Simon two-stage design will be used to assess treatment efficacy. The study will be conducted in four different clinical cohorts separated by prior exposure to enzalutamide or abiraterone acetate, and prior response to the agent (37 patients per cohort).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Patients must have documented histological or cytological evidence of adenocarcinoma of the prostate.
  2. Patients must have received enzalutamide or abiraterone for CRPC. Patients who have received combination enzalutamide/abiraterone or combination ARN509/abiraterone as part of ongoing clinical trials are allowed and will be included in "Prior Abiraterone" arm of this study. Prior treatment with sequential enzalutamide-abiraterone or abiraterone-enzalutamide will not be allowed. Prior treatment with first-generation AR antagonists (i.e., bicalutamide, nilutamide, flutamide) before abiraterone or enzalutamide is allowed.
  3. Patients must have demonstrated disease progression while on enzalutamide and/or abiraterone.

    Progressive disease is defined by one or more of the following:

    • A rise in PSA on two successive determinations at least one week apart and PSA level ≥2ng/ml.
    • Soft-tissue progression defined by RECIST 1.1
    • Bone disease progression defined by PCWG2 with two or more new lesions on bone scan
  4. Patients must have a minimum serum PSA level of ≥2 ng/ml that is rising based on the PCWG2 criteria.
  5. Patients must be ≥18 years of age.
  6. Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]).
  7. Patients must have undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least 3 months prior to drug initiation. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study.
  8. Patients must have an ECOG Performance Score of 0-1.
  9. Patients 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
  10. Patients must have adequate hepatic function as evidenced by AST/ALT levels <3X the ULN and bilirubin levels of <2.0 mg/dl.
  11. Patients must have adequate renal function as evidenced by a serum creatinine of <2.0 mg/dl.
  12. Patients must have K+ >3.5 mEq/l.
  13. Patients or their legal representatives must be able to provide written informed consent.
  14. Patients must have discontinued enzalutamide or abiraterone/prednisolone ≥4 weeks prior to study drug initiation.
  15. Patients who have partners of child-bearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) during the treatment period and for 90 days after last dose of VT-464. Patients must also agree to not donate sperm through 90 days following the last dose of VT-464.

Exclusion Criteria

  1. 1. Patients who have received prior cytotoxic chemotherapy for castration-resistant prostate cancer. Prior docetaxel for castration-sensitive disease is permitted.
  2. Patients who have received TAK-700 (Orteronel®), TOK-001 (Galeterone®), ARN-509 or any other therapeutic investigational product directed towards the androgen receptor (AR) or androgen biosynthesis. Patients who receive ARN-509 in combination with abiraterone as part of a clinical trial are allowed.
  3. Patients who have received ketoconazole, aminoglutethimide, or high-dose estrogen for CRPC.
  4. Patients who have completed sipuleucel-T (Provenge ®) treatment within 30 days of study drug initiation.
  5. Patients on 5 alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 3 months from study drug initiation.
  6. Patients who require pharmacologic or replacement doses of systemic corticosteroids or who have received systemic corticosteroids within 30 days of study drug initiation; use of topical, inhaled or ophthalmic steroids is permitted.
  7. Patients who have received any therapeutic investigational agent within 2 weeks of study drug initiation.
  8. Patients who have received palliative radiotherapy within 4 weeks of study drug initiation.
  9. Patients who have received herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity (e.g., saw palmetto, PC-SPES, PC-HOPE, St. John's wort, selenium supplements, grape seed extract, etc.) within 4 weeks of study drug initiation or plans to initiate treatment with these products/alternative therapies during the entire duration of the study.
  10. Patients with active CNS metastases from prostate cancer. Patients with treated epidural disease are eligible to enroll. Patients with treated brain metastases can be included as long as >4 weeks have elapsed since last treatment (radiotherapy or surgery) for brain metastases, the patient is neurologically and radiographically stable, and is not receiving corticosteroids for brain metastases. Patients with untreated brain metastases are excluded. Brain imaging (CT or MRI) is not required at baseline if brain metastases are not clinically suspected.
  11. Patients with a history of adrenal insufficiency. Patients who have received systemic corticosteroids for >2 weeks within 6 months of study drug initiation (including those receiving prednisolone with abiraterone) must have adrenal insufficiency ruled out by a morning plasma cortisol concentration ≥500 nmol/l or a plasma cortisol response to an ACTH stimulation test that is deemed clinically normal.
  12. Patients with a history within the last 3 years of another invasive malignancy (excluding non-melanoma skin cancer).
  13. Patients 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 patient may be enrolled.
  14. Patients with a history of clinically significant cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes and second degree or third degree atrioventricular heart block without a permanent pacemaker in place. Patients with resolved or rate-controlled atrial fibrillation/atrial flutter are allowed.
  15. Patients with NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction/acute coronary syndrome within the preceding 6 months.
  16. Patients with diabetes mellitus who have had more than 2 episodes of diabetic ketoacidosis in the preceding 12 months.
  17. Inadequately controlled hypertension (defined as blood pressure >150mmHg systolic and/or >100 mmHg diastolic despite antihypertensive medication) or any history of hypertensive crisis or hypertensive encephalopathy.
  18. Patients with a history of seizure within the past 2 years or those who require prophylactic anti-seizure medications are excluded.
  19. History of loss of consciousness or transient ischemic attack within 12 months before study drug initiation.
  20. Patients who have known active HIV, Hepatitis B, or Hepatitis C infections.
  21. Patients with any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the Investigator would preclude safe participation in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02445976

Contacts
Contact: Joel Eisner, Ph.D. 919-237-9536

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35249
Contact: Gurudatta Naik       alkanand@uab.edu   
Contact: Yvonne Waithaka    (205)934-9972    yvonnew@uab.edu   
Principal Investigator: Guru Sonpavde, MD         
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85054
Contact: Jennifer Roedig    480-301-4446    Roedig.Jennifer@mayo.edu   
Contact: Shelly Perez    480-301-9191    Perez.Rochelle@mayo.edu   
Principal Investigator: Alan Bryce, MD         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06519
Contact: Laura Bankowski    203-737-4496    Laura.bankowski@yale.edu   
Principal Investigator: Daniel Petrylak, MD         
United States, Florida
Mofitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Margaret Penichet    813-745-8086    Margaret.penichet@moffitt.org   
Contact: Inez Sims, RN    813-745-3982    inez.sims@moffitt.org   
Principal Investigator: Jingsong Zhang, MD         
United States, Louisiana
Tulane University Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Gaynelle Davis    504-988-6770    Gdavis7@tulane.edu   
Principal Investigator: Alan Sartor, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Flanagan    617-582-8313    David_Flanagan@dfci.harvard.edu   
Contact: Sarah Cronholm       SarahM_Cronholm@DFCI.HARVARD.EDU   
Principal Investigator: Mary-Ellen Taplin, MD         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Brenda Dickow    313-576-9372    dickowb@karmanos.org   
Contact: Amy Wayne       waynea@karmanos.org   
Principal Investigator: Ulka Vaishampayan, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Erin Zielinski, CCRP    612-624-0937    eezielin@umn.edu   
Contact: Stephanie Merek    612-624-5949    merek001@umn.edu   
Principal Investigator: Shilpa Gupta, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Suzanne Shaffer    314-747-1343    sshaffer@DOM.wustl.edu   
Contact: Emily Milford       EMILFORD@DOM.wustl.edu   
Principal Investigator: Joel Picus, MD         
United States, Nebraska
GU Research Network Recruiting
Omaha, Nebraska, United States, 68130
Contact: Lyndsay Morton    402-697-2214    lmorton@gucancer.com   
Contact: Diane Tichota       dtichota@gucancer.com   
Principal Investigator: Luke Nordquist, MD         
United States, New Mexico
New Mexico Cancer Care Alliance Recruiting
Albuquerque, New Mexico, United States, 87106
Principal Investigator: Richard Lauer, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Shady Prestol    646-227-2140    prestols@mskcc.org   
Contact: Alex Butler       butlera2@mskcc.org   
Principal Investigator: Howard Scher, MD         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Ellen Cohen    919-843-2448    Ellen_cohen@med.unc.edu   
Contact: Linda Wydsch       linda_wydysh@med.unc.edu   
Principal Investigator: Young Whang, MD         
United States, South Carolina
Carolina Urologic Research Center Recruiting
Myrtle Beach, South Carolina, United States, 29572
Contact: Salie Hinson    843-449-1010 ext 261    shinson@atlanticurologyclinics.com   
Contact: Jennifer Griffith    843-449-1010 ext 316    jgriffith@atlanticurologyclinics.com   
Principal Investigator: Neal Shore, MD         
United States, Virginia
Virginia Oncology Associates Recruiting
Hampton, Virginia, United States, 23666
Contact: Wendi Gobhardt    757-213-5813    wendi.gobhardt@usoncology.com   
Contact: Stephanie Griffith    757-213-5616    Stephanie.Griffith@usoncology.com   
Principal Investigator: Mark Fleming, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Kelly Crowder    206-288-7486    kcrowder@seattlecca.org   
Contact: Jessica Johnson    206-288-7615    jojohnso@seattlecca.org   
Principal Investigator: Bruce Montgomery, MD         
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53715
Contact: Mary Jane Staab    608-263-7107    mjs@medicine.wisc.edu   
Contact: Jamie Wiepz, BS       jkwiepz@uwcarbone.wisc.edu   
Principal Investigator: Christos Kyriakopoulos, MD         
Sponsors and Collaborators
Innocrin Pharmaceutical
Prostate Cancer Foundation
Prostate Cancer Clinical Trials Consortium
  More Information

Responsible Party: Innocrin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02445976     History of Changes
Other Study ID Numbers: INO-VT-464-CL-003
VMT-VT-464-CL-003 ( Other Identifier: Innocrin )
Study First Received: May 13, 2015
Last Updated: September 2, 2016

Keywords provided by Innocrin Pharmaceutical:
mCRPC
metastatic
castration-resistant prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 25, 2017