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

Metastatic Castration-Resistant Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02705469
• Other study ID #: ZEN003694-001
• Status: Completed
• Phase: Phase 1
• First received: February 10, 2016
• Last updated: November 16, 2017
• Start date: May 2016
• Est. completion date: October 2017

Study information

• Verified date: November 2017
• Source: Zenith Epigenetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ZEN003694

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Zenith Epigenetics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria		From screening up to 24 months
Secondary	Evaluate radiographic response rate by PCWG2 criteria		From screening up to 24 months
Secondary	Evaluate median progression-free survival by PCWG2 criteria		From screening up to 24 months
Secondary	Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only		From screening up to 12 months