A Randomized, Double-blind, Placebo Controlled Phase III Study of Darolutamide (ODM-201) Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 1,306
- 主要终点
- OS From Date of Randomization Until Death From Any Cause - Number of Events
研究概览
简要总结
The purpose of the study is to assess the efficacy and safety of BAY1841788 (darolutamide (ODM-201)) in combination with standard androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone sensitive prostate cancer.
详细描述
This is a randomized, double-blind, placebo-controlled, multicenter phase III study. The study population will consist of approximately 1300 subjects with metastatic hormone sensitive prostate cancer (mHSPC), who will be randomized (1:1 ratio) to receive 600 mg (2 x 300 mg tablets) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total daily dose of 1200 mg, in addition to standard androgen deprivation therapy (ADT) and docetaxel. Subjects will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels. All subjects will be treated with ADT as standard therapy. Six cycles of docetaxel will be administered after randomization.
The subjects considered for inclusion in the study will have metastatic prostate cancer and will be candidates for ADT and docetaxel.
Treatment with darolutamide (ODM-201)/placebo will be administered until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, until subject withdraws consent, withdrawal from the study at the discretion of the investigator or his/her designated associate(s), death, non-compliance, or if sponsor terminates the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of prostate.
- •Metastatic disease
- •Candidates for ADT and docetaxel.
- •Started ADT with or without first generation anti androgen, but no longer than 12 weeks before randomization
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow, liver and renal function
排除标准
- •Prior treatment with: LHRH agonist/antagonists; second generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide (ODM-201), other investigational AR inhibitors; CYP17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer; chemotherapy or immunotherapy for prostate cancer prior to randomization.
- •Treatment with radiotherapy/radiopharmaceuticals within 2 weeks before randomization.
- •Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
- •Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed 5 years before randomization and from which the subject has been disease-free
- •Gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study treatment.
- •Inability to swallow oral medications
研究组 & 干预措施
Placebo + standard ADT + Docetaxel
Co-administration of Placebo matching BAY 1841788 / darolutamide (ODM-201) tablets, standard ADT and docetaxel
干预措施: Docetaxel (Drug)
BAY1841788 /darolutamide (ODM-201)+standard ADT+Docetaxel
Co-administration of BAY 1841788 / darolutamide (ODM-201), standard ADT and docetaxel
干预措施: BAY1841788 / darolutamide (ODM-201) (Drug)
BAY1841788 /darolutamide (ODM-201)+standard ADT+Docetaxel
Co-administration of BAY 1841788 / darolutamide (ODM-201), standard ADT and docetaxel
干预措施: Standard ADT (androgen deprivation therapy) (Drug)
BAY1841788 /darolutamide (ODM-201)+standard ADT+Docetaxel
Co-administration of BAY 1841788 / darolutamide (ODM-201), standard ADT and docetaxel
干预措施: Docetaxel (Drug)
Placebo + standard ADT + Docetaxel
Co-administration of Placebo matching BAY 1841788 / darolutamide (ODM-201) tablets, standard ADT and docetaxel
干预措施: Standard ADT (androgen deprivation therapy) (Drug)
Placebo + standard ADT + Docetaxel
Co-administration of Placebo matching BAY 1841788 / darolutamide (ODM-201) tablets, standard ADT and docetaxel
干预措施: Placebo (Drug)
结局指标
主要结局
OS From Date of Randomization Until Death From Any Cause - Number of Events
时间窗: From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
Overall survival (OS) was defined as the time from the date of randomization until death from any cause. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study.
OS From Date of Randomization Until Death From Any Cause - Month
时间窗: From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study. Median, percentile and other 95% CIs were computed using Kaplan-Meier estimates. NA = Value cannot be estimated due to censored data
次要结局
- Number of Participants With TEAEs(From the first dose of darolutamide or placebo until 30 days after the last dose of darolutamide or placebo administration up to cut-off date for the final completion analysis 11 APR 2023 (approximately 77 months))
- Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events(From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Castration-Resistant Prostate Cancer (CRPC) - Month(From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Pain Progression - Number of Events(From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Pain Progression - Month(From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months)
- Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events(From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months)
- Symptomatic Skeletal Event Free Survival (SSE-FS) - Month(From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to First Symptomatic Skeletal Event (SSE) - Number of Events(From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to First Symptomatic Skeletal Event (SSE) - Month(From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events(From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Initiation of Subsequent Antineoplastic Therapy - Month(From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Worsening of Disease-Related Physical Symptoms - Number of Events(From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Worsening of Disease-Related Physical Symptoms - Month(From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events(From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months)
- Time to Initiation of Opioid Use for ≥7 Consecutive Days - Month(From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months)