Clinical trial NCT02705469: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Zenith Epigenetics
Sponsor class: INDUSTRY
First posted: 2016-03-10
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: For dose escalation only: Incidence of dose-limiting toxicities (DLT)
timeFrame: Cycle 1 (Day 1 thru Day 28)
measure: For dose escalation and dose confirmation: Incidence of treatment-related adverse events (AE) and treatment-related serious adverse events (SAE)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694
timeFrame: 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: Measure the PK parameter: Cmax of ZEN003694
timeFrame: 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: Measure the PK parameter: Cmin of ZEN003694
timeFrame: 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: Measure the PK parameter: Tmax of ZEN003694
timeFrame: 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: Measure the PK parameter: t1/2 of ZEN003694
timeFrame: 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: Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria
timeFrame: From screening up to 24 months
measure: Evaluate radiographic response rate by PCWG2 criteria
timeFrame: From screening up to 24 months
measure: Evaluate median progression-free survival by PCWG2 criteria
timeFrame: From screening up to 24 months
measure: Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only
timeFrame: From screening up to 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hampton
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
References: