Metastatic Castration-Resistant Prostate Cancer
Conditions
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
Brief summary
This is an open label, Phase 1, dose escalation and dose confirmation study of ZEN003694 in patients with mCRPC.
Interventions
DRUGZEN003694
Sponsors
Zenith Epigenetics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| For dose escalation only: Incidence of dose-limiting toxicities (DLT) | 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) | Up to 24 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure the PK parameter: Cmin of ZEN003694 | 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 minimum or trough plasma concentration of drug. |
| Measure the PK parameter: Tmax of ZEN003694 | 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 PK parameter: t1/2 of ZEN003694 | 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 | t/12 is defined as the half-life of drug. |
| Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694 | 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). |
| 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 | — |
| Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria | From screening up to 24 months | — |
| Measure the PK parameter: Cmax of ZEN003694 | 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 maximum or peak plasma concentration of drug. |
Countries
United States
Outcome results
None listed