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

A Phase 1 Safety and Tolerability Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer

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

Study Overview

• Status: Completed
• Conditions: Metastatic Castration-Resistant Prostate Cancer
• Intervention / Treatment: Drug: ZEN003694

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
      • University of California Los Angeles Medical Center
    • San Francisco, California, United States
      • University of California San Francisco Medical Center
  • Michigan
    • Detroit, Michigan, United States
      • Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health & Science University
  • Virginia
    • Hampton, Virginia, United States
      • Virginia Oncology Associates
    • Norfolk, Virginia, United States
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Dose Confirmation - ZEN003694 Single Agent; ZEN003694 will be administered orally as a single agent once daily in 28-day cycles, enrolling mCRPC patients.	Drug: ZEN003694

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Cycle 1 (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)		Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694	AUC is defined as the area under the curve (plasma concentration of drug over time).	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
Measure the PK parameter: Cmax of ZEN003694	Cmax is defined as maximum or peak plasma concentration of drug.	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
Measure the PK parameter: Cmin of ZEN003694	Cmin is defined as minimum or trough plasma concentration of drug.	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
Measure the PK parameter: Tmax of ZEN003694	Tmax is defined as the time from dosing to the maximum plasma concentration.	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
Measure the PK parameter: t1/2 of ZEN003694	t/12 is defined as the half-life of drug.	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
Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria		From screening up to 24 months
Evaluate radiographic response rate by PCWG2 criteria		From screening up to 24 months
Evaluate median progression-free survival by PCWG2 criteria		From screening up to 24 months
Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only		From screening up to 12 months

Collaborators and Investigators

• Sponsor: Zenith Epigenetics

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: February 10, 2016
• First Submitted That Met QC Criteria: March 4, 2016
• First Posted (Estimate): March 10, 2016

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Prostate Cancer; Phase 1; Epigenetics; ZEN003694; Pharmacokinetics (PK); Pharmacodynamics (PD); ZEN-3694; Bromodomain; Metastatic Castration-Resistant Prostate Cancer (mCRPC); Metastatic Castrate-Resistant Prostate Cancer; BET inhibitor (BETi)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: ZEN003694-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO