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A Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer

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: NCT02711956
Recruitment Status : Active, not recruiting
First Posted : March 17, 2016
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Zenith Epigenetics

Tracking Information
First Submitted Date  ICMJE March 14, 2016
First Posted Date  ICMJE March 17, 2016
Last Update Posted Date July 24, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2016)
  • For dose escalation only: Incidence of dose-limiting toxicities (DLT) [ Time Frame: Cycle 1 (Day 1 thru Day 28) ]
    A DLT is a treatment-related, clinically significant adverse event or laboratory abnormality occurring during the first cycle of treatment (Day 1 thru Day 28).
  • For dose escalation and dose confirmation: Incidence of treatment-related adverse events (AE) and treatment-related serious adverse events (SAE) [ Time Frame: Up to 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2016)
  • Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694 administered in combination with enzalutamide [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 2 Day 1: pre-dose ]
    AUC is defined as the area under the curve (plasma concentration of drug over time).
  • Measure the pharmacokinetic (PK) parameter: Cmax of ZEN003694 administered in combination with enzalutamide [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 2 Day 1: pre-dose ]
    Cmax is defined as the maximum or peak plasma concentration of drug.
  • Measure the pharmacokinetic (PK) parameter: Cmin of ZEN003694 administered in combination with enzalutamide [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 2 Day 1: pre-dose ]
    Cmin is defined as the minimum or trough plasma concentration of drug.
  • Measure the pharmacokinetic (PK) parameter: Tmax of ZEN003694 administered in combination with enzalutamide [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 2 Day 1: pre-dose ]
    Tmax is defined as the time from dosing to the maximum plasma concentration.
  • Measure the pharmacokinetic (PK) parameter: t1/2 of ZEN003694 administered in combination with enzalutamide [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 2 Day 1: pre-dose ]
    t1/2 is defined as the half-life of drug.
  • Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria [ Time Frame: From screening up to 18 months ]
  • Evaluate radiographic response rate by PCWG2 criteria [ Time Frame: From screening up to 18 months ]
  • Evaluate median progression-free survival by PCWG2 criteria [ Time Frame: From screening up to 18 months ]
  • Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only [ Time Frame: From screening up to 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer
Official Title  ICMJE A Phase 1b/2a Safety and Tolerability Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer
Brief Summary This is an open label, non-randomized, Phase 1b/2a, dose escalation and dose confirmation study of ZEN003694 in combination with enzalutamide in patients with mCRPC.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Castration-Resistant Prostate Cancer
Intervention  ICMJE
  • Drug: ZEN003694
  • Drug: Enzalutamide
    Other Names:
    • XTANDI
    • MDV3100
Study Arms  ICMJE Experimental: DE and DC - ZEN003694 in Combination with Enzalutamide

Dose Escalation (DE) and Dose Confirmation (DC): ZEN003694 will be administered orally once daily with enzalutamide in 28-day cycles, enrolling mCRPC patients.

Patients are either enzalutamide-naïve with prior progression on abiraterone by Prostate Cancer Working Group 2 (PCWG2) criteria or are currently receiving enzalutamide who have experienced prostate-specific antigen (PSA) progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. For the latter, patients may or may not have experienced prior progression on abiraterone.

Interventions:
  • Drug: ZEN003694
  • Drug: Enzalutamide
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2016)
58
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males age ≥ 18 years
  2. Metastatic, castrate resistant, histologically confirmed prostate cancer; surgically castrated or continuous medical castration for ≥ 8 weeks prior to screening
  3. Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Adequate laboratory parameters [absolute neutrophil (ANC), platelets, asparate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening
  6. Dose Escalation only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone
  7. Dose Confirmation Cohort A (DC-A) only: Currently receiving enzalutamide as most recent systemic therapy for mCRPC and have experienced PSA progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. Patients may or may not have experienced prior progression on abiraterone.
  8. Dose Confirmation Cohort B (DC-B) only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone

Exclusion Criteria:

  1. Any history of brain metastases or prior seizure or conditions predisposing to seizure activity
  2. Have previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-001)
  3. Have received prior systemic anti-cancer therapy (including abiraterone) or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
  4. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
  5. Radiation therapy within 2 weeks of the first administration of study drug
  6. Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry)
  7. Have received prior investigational anti-androgen therapy, including ARN-509
  8. Currently receiving medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. Strong inducers, inhibitors and substrates must be discontinued at least 7 days prior to the first administration of study drug.
  9. Not a candidate for enzalutamide treatment, in the opinion of the Investigator
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 NCT02711956
Other Study ID Numbers  ICMJE ZEN003694-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zenith Epigenetics
Study Sponsor  ICMJE Zenith Epigenetics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Zenith Epigenetics
Verification Date July 2019

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