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

Официальное название

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

Обзор

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

Вмешательства

• Препарат ZEN003694
  72 mg PO QD
• Препарат Enzalutamide
  160 mg PO QD

Первичные конечные точки

• Cohort A: Radiographic progression-free survival (rPFS) by BICR [Срок оценки: Randomization up to 30 months]

Вторичные конечные точки (12)

• Cohorts A + B: Radiographic progression-free survival (rPFS) by BICR [Срок оценки: Randomization up to 30 months]
• Cohort A: Radiographic progression-free survival (rPFS) by investigator assessment [Срок оценки: Randomization up to 30 months]
• Cohort A + B: Radiographic progression-free survival (rPFS) by investigator assessment [Срок оценки: Randomization up to 30 months]
• Cohort A: Progression-free survival (PFS) by investigator assessment [Срок оценки: Randomization up to 30 months]
• Cohort A + B: Progression-free survival (PFS) by investigator assessment [Срок оценки: Randomization up to 30 months]
• Cohort A: Overall survival (OS) [Срок оценки: Randomization up to 30 months]
• Cohort A + B: Overall survival (OS) [Срок оценки: Randomization up to 30 months]
• Cohort A: PSA50 response rate [Срок оценки: Randomization up to 30 months]
• Cohort A + B: PSA50 response rate [Срок оценки: Randomization up to 30 months]
• Cohort A: Assess efficacy endpoints for patients enrolled in the USA [Срок оценки: Randomization up to 30 months]
• Cohort A + B: Assess efficacy endpoints for patients enrolled in the USA [Срок оценки: Randomization up to 30 months]
• Objective response rate (ORR) [Срок оценки: Randomization up to 30 months]

Критерии участия

Критерии включения

• Males age ≥ 18 years
• Metastatic, castration-resistant, histologically confirmed prostate cancer
• 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
• Have progressed on prior abiraterone treatment by PCWG3 criteria
• Patients who are not candidates for chemotherapy in the opinion of the investigator or patients who decline chemotherapy
• Cohort A only - Patient must meet definition of poor responder to abiraterone by one of the following:

• 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
• Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: < 6 months duration on abiraterone or failure to achieve a PSA50 response
• Cohort B only - Patient must meet definition of responder to abiraterone by one of the following:

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

Критерии исключения

• Any history of brain metastases, prior seizure, conditions predisposing to seizure activity
• Have previously received an investigational BET inhibitor (including previous participation in this study or a study of ZEN003694)
• 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.
• 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)
• 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
• Have received exogenous administration of testosterone therapy since discontinuation of abiraterone.
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 16 центров

• California Research Institute — Los Angeles
• University of California, San Francisco — San Francisco
• Innovative Clinical Research Institute — Whittier
• Colorado Urology — Lakewood
• D&H Cancer Research Center, LLC — Margate
• BRCR Global — Plantation
• Hematology Oncology Clinic — Baton Rouge
• Maryland Oncology Hematology, P.A. — Columbia
• … и ещё 8 центров

Китай · 15 центров

• Anhui Provincial Hospital — Хэфэй
• Chongqing Cancer Hospital — Чунцин
• The First Affiliated Hospital of Xiamen University — Xiamen
• Henan Cancer Hospital — Чжэнчжоу
• Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology — Ухань
• Hubei Cancer Hospital — Ухань
• Hunan Cancer Hospital — Чанша
• Nanjing Drum Tower Hospital — Нанкин
• … и ещё 7 центров

Идентификаторы

NCT: NCT04986423 · ZEN003694-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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