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

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

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

Conditions
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Metastatic Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: ZEN003694


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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