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Trial record 2 of 2 for:    ZEN003694

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Zenith Epigenetics
Sponsor:
Information provided by (Responsible Party):
Zenith Epigenetics
ClinicalTrials.gov Identifier:
NCT02711956
First received: March 14, 2016
Last updated: March 28, 2017
Last verified: March 2017
  Purpose
This is an open label, non-randomized, Phase 1b, dose escalation and dose confirmation study of ZEN003694 in combination with enzalutamide in patients with mCRPC.

Condition Intervention Phase
Metastatic Castration-Resistant Prostate Cancer
Drug: ZEN003694
Drug: Enzalutamide
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1b Safety and Tolerability Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Zenith Epigenetics:

Primary Outcome Measures:
  • For dose escalation only: Incidence of dose-limiting toxicities (DLT) [ Time Frame: 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) [ Time Frame: Up to 18 months ]

Secondary Outcome Measures:
  • Measure the pharmacokinetic (PK) parameter: AUC of ZEN003694 administered in combination with enzalutamide [ Time Frame: 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).

  • Measure the pharmacokinetic (PK) parameter: Cmax of ZEN003694 administered in combination with enzalutamide [ Time Frame: 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 the maximum or peak plasma concentration of drug.

  • Measure the pharmacokinetic (PK) parameter: Cmin of ZEN003694 administered in combination with enzalutamide [ Time Frame: 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 the minimum or trough plasma concentration of drug.

  • Measure the pharmacokinetic (PK) parameter: Tmax of ZEN003694 administered in combination with enzalutamide [ Time Frame: 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 pharmacokinetic (PK) parameter: t1/2 of ZEN003694 administered in combination with enzalutamide [ Time Frame: 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 ]
    t1/2 is defined as the half-life of drug.

  • Evaluate prostate-specific antigen (PSA) response rate by PCWG2 criteria [ Time Frame: From screening up to 18 months ]
  • Evaluate radiographic response rate by PCWG2 criteria [ Time Frame: From screening up to 18 months ]
  • Evaluate median progression-free survival by PCWG2 criteria [ Time Frame: From screening up to 18 months ]
  • Evaluate circulating tumor cell (CTC) response rate during dose confirmation phase only [ Time Frame: From screening up to 12 months ]

Estimated Enrollment: 58
Study Start Date: December 2016
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DE and DC - ZEN003694 in Combination with Enzalutamide

Dose Escalation (DE) and Dose Confirmation (DC): ZEN003694 will be administered orally once daily with enzalutamide in 28-day cycles, enrolling mCRPC patients.

Patients are either enzalutamide-naïve with prior progression on abiraterone by Prostate Cancer Working Group 2 (PCWG2) criteria or are currently receiving enzalutamide who have experienced prostate-specific antigen (PSA) progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. For the latter, patients may or may not have experienced prior progression on abiraterone.

Drug: ZEN003694 Drug: Enzalutamide
Other Names:
  • XTANDI
  • MDV3100

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Adequate laboratory parameters [absolute neutrophil (ANC), platelets, asparate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening
  6. Dose Escalation only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone
  7. Dose Confirmation Cohort A (DC-A) only: Currently receiving enzalutamide as most recent systemic therapy for mCRPC and have experienced PSA progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. Patients may or may not have experienced prior progression on abiraterone.
  8. Dose Confirmation Cohort B (DC-B) only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone

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 ZEN003694-001)
  3. Have received prior systemic anti-cancer therapy (including abiraterone) 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 the 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. Have received prior investigational anti-androgen therapy, including ARN-509
  8. Currently receiving medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. Strong inducers, inhibitors and substrates must be discontinued at least 7 days prior to the first administration of study drug.
  9. Not a candidate for enzalutamide treatment, in the opinion of the Investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02711956

Contacts
Contact: Zenith Study Team ZEN003694-002@zenithepigenetics.com

Locations
United States, California
University of California Los Angeles Medical Center Recruiting
Los Angeles, California, United States
University of California San Francisco Medical Center Recruiting
San Francisco, California, United States
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States
Karmanos Cancer Institute Recruiting
Farmington Hills, Michigan, United States
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States
United States, Virginia
Virginia Oncology Associates Recruiting
Hampton, Virginia, United States
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States
Sponsors and Collaborators
Zenith Epigenetics
  More Information

Responsible Party: Zenith Epigenetics
ClinicalTrials.gov Identifier: NCT02711956     History of Changes
Other Study ID Numbers: ZEN003694-002
Study First Received: March 14, 2016
Last Updated: March 28, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Zenith Epigenetics:
ZEN003694
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Phase 1b
Prostate Cancer
Pharmacokinetics (PK)
ZEN-3694
Metastatic Castrate-Resistant Prostate Cancer
BET inhibitor (BETi)
Bromodomain
Pharmacodynamics (PD)
Enzalutamide
XTANDI
MDV3100
Epigenetics

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on May 25, 2017