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

NCT02705469 | Completed Phase 1

• 1 other identifier: ZEN003694-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 8

Brief Summary

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

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

Dose Escalation and Dose Confirmation - ZEN003694 Single Agent

EXPERIMENTAL

ZEN003694 will be administered orally as a single agent once daily in 28-day cycles, enrolling mCRPC patients.

Drug: ZEN003694

Interventions

ZEN003694 DRUG

Dose Escalation and Dose Confirmation - ZEN003694 Single Agent

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zenith Epigenetics: lead

Study Sites (8)

University of California Los Angeles Medical Center

Los Angeles, California, United States

Location

University of California San Francisco Medical Center

San Francisco, California, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, United States

Location

Karmanos Cancer Institute

Farmington Hills, Michigan, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Location

Oregon Health & Science University

Portland, Oregon, United States

Location

Virginia Oncology Associates

Hampton, Virginia, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: March 10, 2016
• Study Start: May 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: November 20, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)