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

NCT ID: NCT02711956

Last Updated: 2021-11-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2019-11-30

Brief Summary

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This is an open label, non-randomized, Phase 1b/2a, dose escalation and dose confirmation study of ZEN003694 in combination with enzalutamide in patients with mCRPC.

Detailed Description

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Conditions

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Metastatic Castration-Resistant Prostate Cancer

Keywords

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Metastatic Castration-Resistant Prostate Cancer (mCRPC) Phase 1b/2a Prostate Cancer Pharmacokinetics (PK) ZEN003694 ZEN-3694 Metastatic Castrate-Resistant Prostate Cancer BET inhibitor (BETi) Bromodomain Pharmacodynamics (PD) Enzalutamide XTANDI MDV3100 Epigenetics

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Two patient populations will be enrolled in DE and DC. Cohort A: Patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria who were receiving a stable dose of enzalutamide at the time of study entry. Cohort B: Patients who were enzalutamide-naïve with prior progression on abiraterone by Prostate Cancer Working Group 2 (PCWG2) criteria.

Group Type EXPERIMENTAL

ZEN003694

Intervention Type DRUG

Enzalutamide

Intervention Type DRUG

Interventions

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ZEN003694

Intervention Type DRUG

Enzalutamide

Intervention Type DRUG

Other Intervention Names

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XTANDI MDV3100

Eligibility Criteria

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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 Cohort DE-A: Prior progression on enzalutamide or apalutamide at any time by PCWG2 criteria and receiving a stable dose of enzalutamide at the start of study treatment.
7. Dose Escalation Cohort DE-B: Enzalutamide-naïve and apalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and receiving a stable dose of enzalutamide at the start of study treatment.
8. 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.
9. 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Zenith Epigenetics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California Los Angeles Medical Center

Los Angeles, California, United States

Site Status

University of California San Francisco Medical Center

San Francisco, California, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Karmanos Cancer Institute

Farmington Hills, Michigan, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Weill Cornell Medicine - New York Presbyterian

New York, New York, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ZEN003694-002

Identifier Type: -

Identifier Source: org_study_id