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

Primary Purpose

Metastatic Castration-Resistant Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ZEN003694
Sponsored by
Zenith Epigenetics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Castration-Resistant Prostate Cancer focused on measuring Metastatic Castration-Resistant Prostate Cancer (mCRPC), Phase 1, Prostate Cancer, Pharmacokinetics (PK), ZEN003694, ZEN-3694, Metastatic Castrate-Resistant Prostate Cancer, BET inhibitor (BETi), Bromodomain, Pharmacodynamics (PD), Epigenetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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. Prior progression on one or more androgen-receptor/androgen-synthesis inhibitor therapies (e.g. abiraterone, enzalutamide, apalutamide, TAK-700 and/or galeterone) by Prostate Cancer Working Group 2 (PCWG2) criteria. Prior progression on bicalutamide/nilutamide/flutamide/ketoconazole alone is not allowed.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Adequate laboratory parameters [absolute neutrophil (ANC), platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening

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 ZEN003694-002)
  3. Have received prior systemic anti-cancer therapy 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 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. Currently receiving medications known to be strong inducers or inhibitors of CYP3A4 with a narrow therapeutic window. Strong inducers and inhibitors of CYP3A4 with narrow therapeutic ranges must be discontinued at least 7 days prior to the first administration of study drug.

Sites / Locations

  • University of California Los Angeles Medical Center
  • University of California San Francisco Medical Center
  • Karmanos Cancer Institute
  • Karmanos Cancer Institute
  • Memorial Sloan Kettering Cancer Center
  • Oregon Health & Science University
  • Virginia Oncology Associates
  • Virginia Oncology Associates

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation and Dose Confirmation - ZEN003694 Single Agent

Arm Description

ZEN003694 will be administered orally as a single agent once daily in 28-day cycles, enrolling mCRPC patients.

Outcomes

Primary Outcome Measures

For dose escalation only: Incidence of dose-limiting toxicities (DLT)
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)

Secondary Outcome Measures

Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694
AUC is defined as the area under the curve (plasma concentration of drug over time).
Measure the PK parameter: Cmax of ZEN003694
Cmax is defined as maximum or peak plasma concentration of drug.
Measure the PK parameter: Cmin of ZEN003694
Cmin is defined as minimum or trough plasma concentration of drug.
Measure the PK parameter: Tmax of ZEN003694
Tmax is defined as the time from dosing to the maximum plasma concentration.
Measure the PK parameter: t1/2 of ZEN003694
t/12 is defined as the half-life of drug.
Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria
Evaluate radiographic response rate by PCWG2 criteria
Evaluate median progression-free survival by PCWG2 criteria
Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only

Full Information

First Posted
February 10, 2016
Last Updated
November 16, 2017
Sponsor
Zenith Epigenetics
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1. Study Identification

Unique Protocol Identification Number
NCT02705469
Brief Title
A Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer
Official Title
A Phase 1 Safety and Tolerability Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zenith Epigenetics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an open label, Phase 1, dose escalation and dose confirmation study of ZEN003694 in patients with mCRPC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-Resistant Prostate Cancer
Keywords
Metastatic Castration-Resistant Prostate Cancer (mCRPC), Phase 1, Prostate Cancer, Pharmacokinetics (PK), ZEN003694, ZEN-3694, Metastatic Castrate-Resistant Prostate Cancer, BET inhibitor (BETi), Bromodomain, Pharmacodynamics (PD), Epigenetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation and Dose Confirmation - ZEN003694 Single Agent
Arm Type
Experimental
Arm Description
ZEN003694 will be administered orally as a single agent once daily in 28-day cycles, enrolling mCRPC patients.
Intervention Type
Drug
Intervention Name(s)
ZEN003694
Primary Outcome Measure Information:
Title
For dose escalation only: Incidence of dose-limiting toxicities (DLT)
Description
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).
Time Frame
Cycle 1 (Day 1 thru Day 28)
Title
For dose escalation and dose confirmation: Incidence of treatment-related adverse events (AE) and treatment-related serious adverse events (SAE)
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694
Description
AUC is defined as the area under the curve (plasma concentration of drug over time).
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
Title
Measure the PK parameter: Cmax of ZEN003694
Description
Cmax is defined as maximum or peak plasma concentration of drug.
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
Title
Measure the PK parameter: Cmin of ZEN003694
Description
Cmin is defined as minimum or trough plasma concentration of drug.
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
Title
Measure the PK parameter: Tmax of ZEN003694
Description
Tmax is defined as the time from dosing to the maximum plasma concentration.
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
Title
Measure the PK parameter: t1/2 of ZEN003694
Description
t/12 is defined as the half-life of drug.
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
Title
Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria
Time Frame
From screening up to 24 months
Title
Evaluate radiographic response rate by PCWG2 criteria
Time Frame
From screening up to 24 months
Title
Evaluate median progression-free survival by PCWG2 criteria
Time Frame
From screening up to 24 months
Title
Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only
Time Frame
From screening up to 12 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males age ≥ 18 years Metastatic, castrate resistant, histologically confirmed prostate cancer; surgically castrated or continuous medical castration for ≥ 8 weeks prior to screening Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug Prior progression on one or more androgen-receptor/androgen-synthesis inhibitor therapies (e.g. abiraterone, enzalutamide, apalutamide, TAK-700 and/or galeterone) by Prostate Cancer Working Group 2 (PCWG2) criteria. Prior progression on bicalutamide/nilutamide/flutamide/ketoconazole alone is not allowed. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate laboratory parameters [absolute neutrophil (ANC), platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening Exclusion Criteria: Any history of brain metastases or prior seizure or conditions predisposing to seizure activity Have previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-002) Have received prior systemic anti-cancer therapy or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry Radiation therapy within 2 weeks of first administration of study drug 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) Currently receiving medications known to be strong inducers or inhibitors of CYP3A4 with a narrow therapeutic window. Strong inducers and inhibitors of CYP3A4 with narrow therapeutic ranges must be discontinued at least 7 days prior to the first administration of study drug.
Facility Information:
Facility Name
University of California Los Angeles Medical Center
City
Los Angeles
State/Province
California
Country
United States
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
Karmanos Cancer Institute
City
Farmington Hills
State/Province
Michigan
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Virginia Oncology Associates
City
Hampton
State/Province
Virginia
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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