Clinical Trial 18492

Cancer Type: Genitourinary
Interventions:VT-464 (Seviteronel)

Study Type: Treatment
Phase of Study: Phase II


    Study 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


    The purpose of this study is to determine how well the cancer is responding to study treatment with VT-464. The study will also examine the safety of VT-464. Finally, investigators will be studying different properties of the cancer before study treatment to look for clues which may help us know which patients are most likely to respond to this drug in the future.


    5.1 Primary Objective: To determine the proportion of patients who have >=50% PSA decline at or within 12 weeks of starting treatment with VT-464. 5.2 Secondary Objectives: To measure the proportion of patients who have >=50% PSA decline at 12 weeks from start of treatment with VT-464. To determine median rPFS and 6-month rPFS rate. To determine radiologic response rate. To determine overall survival (OS). To determine safety and tolerability. 5.3 Exploratory Objective: To associate predictive biomarkers (Table 1) with clinical outcomes to VT-464 in CRPC patients who have progressed while on enzalutamide or abiraterone.

    Inclusion Criteria

  • Must have documented histological or cytological evidence of adenocarcinoma of the prostate
  • Must have received enzalutamide or abiraterone for Castration-Resistant Prostate Cancer (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.
  • 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.
  • Must have a minimum serum Prostatic Specific Antigen (PSA) level of ≥2 ng/ml that is rising based on the Prostate-Cancer Working Group 2 (PCWG2) criteria
  • Must be ≥18 years of age
  • Must have castrate levels of testosterone (less than 50 ng/dl [1.74 nmol/l])
  • 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.
  • Must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1
  • Must have adequate hematopoietic function
  • Must have adequate hepatic function
  • Must have adequate renal function
  • Must have serum K+ >3.5 mEq/l.
  • Participants or their legal representatives must be able to provide written informed consent.
  • Must have discontinued enzalutamide or abiraterone/prednisolone ≥4 weeks prior to study drug initiation
  • Participants who have partners of child-bearing potential must be willing to use at least two forms of effective birth control during the treatment period and for 90 days after last dose of VT-464. Participants must also agree to not donate sperm through 90 days following the last dose of VT-464.

  • Exclusion Criteria

  • Have received prior cytotoxic chemotherapy for castration-resistant prostate cancer. Prior docetaxel for castration-sensitive disease is permitted.
  • 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.
  • Have received ketoconazole, aminoglutethimide, or high-dose estrogen for CRPC.
  • Have completed sipuleucel-T (Provenge ®) treatment within 30 days of study drug initiation.
  • On 5 alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 3 months from study drug initiation.
  • 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.
  • Have received any therapeutic investigational agent within 2 weeks of study drug initiation.
  • Have received palliative radiotherapy within 4 weeks of study drug initiation.
  • Have received herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 4 weeks of study drug initiation or plans to initiate treatment with these products/alternative therapies during the entire duration of the study.
  • Active central nervous system (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.
  • 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.
  • A history within the last 3 years of another invasive malignancy (excluding non-melanoma skin cancer).
  • 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.
  • 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.
  • NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction/acute coronary syndrome within the preceding 6 months.
  • Potential participants with diabetes mellitus who have had more than 2 episodes of diabetic ketoacidosis in the preceding 12 months.
  • Inadequately controlled hypertension or any history of hypertensive crisis or hypertensive encephalopathy.
  • A history of seizure within the past 2 years or those who require prophylactic anti-seizure medications are excluded.
  • History of loss of consciousness or transient ischemic attack within 12 months before study drug initiation.
  • Known active HIV, Hepatitis B, or Hepatitis C infections.
  • Any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the Investigator would preclude safe participation in the study.