NCT02711956

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2016

Typical duration for phase_1

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 17, 2016

Completed
9 months until next milestone

Study Start

First participant enrolled

December 1, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2019

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

August 10, 2021

Completed
Last Updated

November 30, 2021

Status Verified

November 1, 2021

Enrollment Period

2.9 years

First QC Date

March 14, 2016

Results QC Date

June 18, 2021

Last Update Submit

November 2, 2021

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

Metastatic Castration-Resistant Prostate Cancer (mCRPC)Phase 1b/2aProstate CancerPharmacokinetics (PK)ZEN003694ZEN-3694Metastatic Castrate-Resistant Prostate CancerBET inhibitor (BETi)BromodomainPharmacodynamics (PD)EnzalutamideXTANDIMDV3100Epigenetics

Outcome Measures

Primary Outcomes (2)

  • For Dose Escalation: Incidence of Dose-limiting Toxicities (DLT) to Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of ZEN003694 in Combination With Enzalutamide.

    Determination of DLT was made during the first 28 days of treatment in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably, or definitely related to study drug. The MTD reflects the highest dose of ZEN003694 in combination with enzalutamide that did not cause a DLT in more than 1 of 6 patients. The RP2D is the recommended dose of ZEN003694 in combination with enzalutamide as determined in the dose confirmation phase of the study.

    Cycle 1 (Day 1 thru Day 28)

  • For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE)

    Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity of AEs was graded based on the National Cancer Institute's Common Terminology for Adverse Events (V4.03). A serious adverse event (SAE) was any AE that was: fatal; life-threatening; required in-patient hospitalization or prolonged an existing hospitalization; disabling or incapacitating; a congenital anomaly or birth defect; or any other important medical event.

    Cycle 1 Day 1 to 30 days post last dose

Secondary Outcomes (6)

  • Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria

    Screening up to 35 months

  • Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria

    Screening up to 35 months

  • Evaluate Overall Median Progression-free Survival by PCWG2 Criteria

    Screening up to 35 months

  • Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria

    Screening up to 35 months

  • Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide.

    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

  • +1 more secondary outcomes

Study Arms (1)

DE and DC - ZEN003694 in Combination with Enzalutamide

EXPERIMENTAL

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.

Drug: ZEN003694Drug: Enzalutamide

Interventions

ZEN003694DRUG
DE and DC - ZEN003694 in Combination with Enzalutamide
EnzalutamideDRUG
Also known as: XTANDI, MDV3100
DE and DC - ZEN003694 in Combination with Enzalutamide

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate laboratory parameters \[absolute neutrophil (ANC), platelets, asparate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters\] at screening
  • 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.
  • 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.
  • 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.
  • 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.

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 ZEN003694-001)
  • 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
  • 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 the 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)
  • Have received prior investigational anti-androgen therapy, including ARN-509
  • 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.
  • Not a candidate for enzalutamide treatment, in the opinion of the Investigator

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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

Weill Cornell Medicine - New York Presbyterian

New York, New York, United States

Location

Oregon Health & Science University

Portland, Oregon, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Results Point of Contact

Title
Zenith Study Team
Organization
Zenith Epigenetics Ltd
ZEN003694-002@zenithepigenetics.com
(415) 470-5600

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

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

March 14, 2016

First Posted

March 17, 2016

Study Start

December 1, 2016

Primary Completion

November 1, 2019

Study Completion

November 1, 2019

Last Updated

November 30, 2021

Results First Posted

August 10, 2021

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will not share

Locations

US(8)