Clinical trial NCT04986423: ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer
Official title: A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Castration-Resistant Prostate Cancer
Keywords: mCRPC
ZEN003694
ZEN-3694
Bromodomain
BETi
Enzalutamide
Xtandi®
Lead sponsor: Zenith Epigenetics
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Newsoara Biopharma Co., Ltd.
First posted: 2021-08-02
Enrollment: 200
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have progressed on prior abiraterone by PCWG3 criteria. Disease must have progressed on only abiraterone by PCWG3 criteria prior to study entry.

The patient population will be separated into two cohorts:

Cohort A: Patients with poor response to prior abiraterone defined as:

* Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: \< 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone, or;
* Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve PSA50 response while on abiraterone

Cohort B: Patients with response to prior abiraterone, defined as:

* Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL, or;
* Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and confirmed PSA50 response


Eligibility criteria: Inclusion Criteria:

1. Males age ≥ 18 years
2. Metastatic, castration-resistant, histologically confirmed prostate cancer
3. Surgical castration or continuous medical castration for ≥ 8 weeks prior to screening; serum testosterone \< 50 ng/dL confirmed within 4 weeks of first administration of study drug
4. Have progressed on prior abiraterone treatment by PCWG3 criteria
5. Patients who are not candidates for chemotherapy in the opinion of the investigator or patients who decline chemotherapy
6. Cohort A only - Patient must meet definition of poor responder to abiraterone by one of the following:

   1. Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: \< 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone
   2. Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve a PSA50 response
7. Cohort B only - Patient must meet definition of responder to abiraterone by one of the following:

   1. Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL
   2. Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and PSA50 response
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

1. Any history of brain metastases, prior seizure, conditions predisposing to seizure activity
2. Have previously received an investigational BET inhibitor (including previous participation in this study or a study of ZEN003694)
3. Receipt of prior second-generation androgen receptor inhibitors (e.g. enzalutamide, apalutamide, darolutamide, proxalutamide). Receipt of first-generation AR antagonists (e.g. bicalutamide, nilutamide, flutamide) does not count towards this limit.
4. 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 first dose of study drug)
5. Have received prior systemic anti-cancer therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
6. Have received exogenous administration of testosterone therapy since discontinuation of abiraterone.
7. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
8. Radiation therapy within 2 weeks of the first administration of study drug

Primary outcomes:
measure: Cohort A: Radiographic progression-free survival (rPFS) by BICR
timeFrame: Randomization up to 30 months
Secondary outcomes:
measure: Cohorts A + B: Radiographic progression-free survival (rPFS) by BICR
timeFrame: Randomization up to 30 months
measure: Cohort A: Radiographic progression-free survival (rPFS) by investigator assessment
timeFrame: Randomization up to 30 months
measure: Cohort A + B: Radiographic progression-free survival (rPFS) by investigator assessment
timeFrame: Randomization up to 30 months
measure: Cohort A: Progression-free survival (PFS) by investigator assessment
timeFrame: Randomization up to 30 months
measure: Cohort A + B: Progression-free survival (PFS) by investigator assessment
timeFrame: Randomization up to 30 months
measure: Cohort A: Overall survival (OS)
timeFrame: Randomization up to 30 months
measure: Cohort A + B: Overall survival (OS)
timeFrame: Randomization up to 30 months
measure: Cohort A: PSA50 response rate
timeFrame: Randomization up to 30 months
measure: Cohort A + B: PSA50 response rate
timeFrame: Randomization up to 30 months
measure: Cohort A: Assess efficacy endpoints for patients enrolled in the USA
timeFrame: Randomization up to 30 months
measure: Cohort A + B: Assess efficacy endpoints for patients enrolled in the USA
timeFrame: Randomization up to 30 months
measure: Objective response rate (ORR)
timeFrame: Randomization up to 30 months
measure: Patient-reported health status and quality of life (QoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Screening and Day 1 of every 28-day Cycle up to 30 months
measure: Patient-reported health status and quality of life (QoL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Module (EORTC QLQ-PR25).
timeFrame: Screening and Day 1 of every 28-day Cycle up to 30 months
measure: Time to initiation of chemotherapy
timeFrame: Randomization up to 30 months
measure: Time to first skeletal related event (SRE)
timeFrame: Randomization up to 30 months
measure: Measure plasma concentrations of ZEN003694 and the active metabolite ZEN003791
timeFrame: Cycle 1 Day 1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose; Cycle 2 Day1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Lakewood
country: United States
facility: Colorado Urology
state: Colorado
city: Margate
country: United States
facility: D&H Cancer Research Center, LLC
state: Florida
city: Plantation
country: United States
facility: BRCR Global
state: Florida
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic
state: Louisiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: Asheville
country: United States
facility: Messino Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Central South
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotang University
state: Shaanxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
References: