ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer

Metastatic Castration-Resistant Prostate Cancer Clinical Trial

Official title:

A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04986423
• Other study ID #: ZEN003694-201
• Status: Recruiting
• Phase: Phase 2
• Start date: September 8, 2021
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Zenith Epigenetics
• Contact: Zenith Study Team
• Phone: 587-390-7865
• Email: ZEN003694-201[@]zenithepigenetics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ZEN003694
72 mg PO QD
• Enzalutamide
160 mg PO QD

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotang University	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
United States	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	Messino Cancer Center	Asheville	North Carolina
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	Colorado Urology	Lakewood	Colorado
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	BRCR Global	Plantation	Florida
United States	University of California, San Francisco	San Francisco	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
Zenith Epigenetics	Astellas Pharma Inc, Newsoara Biopharma Co., Ltd.

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A: Radiographic progression-free survival (rPFS) by BICR	Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.	Randomization up to 30 months
Secondary	Cohorts A + B: Radiographic progression-free survival (rPFS) by BICR	Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3	Randomization up to 30 months
Secondary	Cohort A: Radiographic progression-free survival (rPFS) by investigator assessment	Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.	Randomization up to 30 months
Secondary	Cohort A + B: Radiographic progression-free survival (rPFS) by investigator assessment	Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.	Randomization up to 30 months
Secondary	Cohort A: Progression-free survival (PFS) by investigator assessment	Time from date of randomization to the date of first disease radiographic progression, clinical progression, or death for any reason. Radiographic progression of disease will be evaluated by RECIST 1.1 and PCWG3 by investigator assessment. Clinical progression is significant pain increase or clinical deterioration that requires initiating another line of treatment.	Randomization up to 30 months
Secondary	Cohort A + B: Progression-free survival (PFS) by investigator assessment	Time from date of randomization to the date of first disease radiographic progression, clinical progression, or death for any reason. Radiographic progression of disease will be evaluated by RECIST 1.1 and PCWG3 by investigator assessment. Clinical progression is significant pain increase or clinical deterioration that requires initiating another line of treatment.	Randomization up to 30 months
Secondary	Cohort A: Overall survival (OS)	Time from date of randomization to the date of death from any cause	Randomization up to 30 months
Secondary	Cohort A + B: Overall survival (OS)	Time from date of randomization to the date of death from any cause	Randomization up to 30 months
Secondary	Cohort A: PSA50 response rate	PSA response is a reduction in serum PSA concentration of =50% from baseline.	Randomization up to 30 months
Secondary	Cohort A + B: PSA50 response rate	PSA response is a reduction in serum PSA concentration of =50% from baseline.	Randomization up to 30 months
Secondary	Objective response rate (ORR)	Proportion of the patients who have either a complete response (CR) or partial response (PR) by RECIST 1.1 criteria who have measurable disease at baseline.	Randomization up to 30 months
Secondary	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)	EORTC QLQ-C30: cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.	Screening and Day 1 of every 28-day Cycle up to 30 months
Secondary	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).	EORTC QLQ-PR25: prostate cancer specific instrument with 25 questions used in conjunction with EORTC QLQ-C30 to assess the participant QoL. Used to evaluate 5 multi-item scales (urinary, bowel, and hormonal treatment-related symptoms, sexual activity, and sexual functioning) and one single item (problems due to incontinence aid use). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.	Screening and Day 1 of every 28-day Cycle up to 30 months
Secondary	Time to initiation of chemotherapy	Time from date of randomization to the first dose of chemotherapy.	Randomization up to 30 months
Secondary	Time to first skeletal related event (SRE)	Time from date of randomization to the first SRE such as pathological fracture, surgery/radiotherapy for pain/prevention of fracture, hypercalcemia, and spinal cord compression.	Randomization up to 30 months
Secondary	Measure plasma concentrations of ZEN003694 and the active metabolite ZEN003791	Plasma concentrations of ZEN003694 and the active metabolite ZEN003791 will be measured.	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