Phase II Study of Neoadjuvant Androgen Deprivation Therapy Plus Abiraterone With or Without Apalutamide for Patients With High-Risk Localized Prostate Cancer Prior to Radical Prostatectomy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Pathologic response
研究概览
简要总结
This is a randomized study to evaluate the efficacy and safety neoadjuvant androgen deprivation therapy with goserelin and abiraterone with or without apalutamide prior to radical prostatectomy for patients diagnosed with localized high-risk prostate cancer.
详细描述
In the prostate specific antigen (PSA) era, about 15% to 20% of patients are diagnosed with high-risk localized disease and radical prostatectomy is a standard therapy for this subgroup of patients. However, despite best local therapy, about 30-60% of high-risk patients will eventually develop biochemical relapse and a significant proportion of these patients may progress with metastatic disease and die from prostate cancer. Currently, there is no data supporting the use of neoadjuvant therapy for patients with high-risk disease since studies failed to demonstrate clinically significant benefit with standard androgen deprivation therapy (ADT). Following improved outcomes in other malignancies with the use of neoadjuvant therapy with active drugs in the metastatic setting, there is a growing interest in evaluating new-generation androgen receptor (AR)-targeted therapy in earlier stages of prostate cancer. Therefore, the goal of this study is to evaluate the efficacy and safety of neoadjuvant therapy with ADT and abiraterone versus maximal androgen blockade using ADT, abiraterone and apalutamide for patients with high-risk localized prostate cancer.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologic confirmed prostatic adenocarcinoma
- •Non-castrate levels of testosterone (> 150 ng/dL)
- •High-risk localized prostate cancer, defined by either:
- •Tumor stage T3 by digital rectal examination, or
- •Primary tumor Gleason score ≥ 8, or
- •PSA ≥ 20 ng/mL
- •Willing to undergo prostatectomy as primary treatment for localized prostate cancer
- •Adequate hematologic, renal and hepatic function:
- •WBC > 3000/uL
- •Platelets > 150,000/uL
- •Creatinine < 2 mg/dL
- •Bilirubin < 1.5 x upper limit of normal (ULN)
- •AST/ALT < 2 x ULN
- •Karnofsky Performance Status (KPS) ≥ 80%
- •Able to swallow the study drugs whole as tablets
排除标准
- •Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
- •Current or prior hormonal therapy, radiation therapy or chemotherapy for prostate cancer
- •Evidence of metastatic disease (M1) on imaging studies
- •Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma
- •Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure
- •History of prior cardiac arrhythmia.
- •Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.
研究组 & 干预措施
ADT and Abiraterone
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
干预措施: Prednisone (Drug)
ADT and Abiraterone
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
干预措施: Goserelin (Drug)
ADT and Abiraterone
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
干预措施: Abiraterone (Drug)
ADT, Abiraterone and Apalutamide
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
- Apalutamide 240 mg, once daily, orally for 3 months.
干预措施: Goserelin (Drug)
ADT, Abiraterone and Apalutamide
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
- Apalutamide 240 mg, once daily, orally for 3 months.
干预措施: Prednisone (Drug)
ADT, Abiraterone and Apalutamide
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
- Apalutamide 240 mg, once daily, orally for 3 months.
干预措施: Abiraterone (Drug)
ADT, Abiraterone and Apalutamide
- Goserelin 10.8 mg, single dose, subcutaneously.
- Abiraterone 1,000 mg, once daily, orally for 3 months.
- Prednisone 5 mg, once daily, orally for 3 months.
- Apalutamide 240 mg, once daily, orally for 3 months.
干预措施: Apalutamide (Drug)
结局指标
主要结局
Pathologic response
时间窗: 3 months
To compare the rate of pathologic complete response (pCR) or pathologic near complete response (pnCR), defined as less than 0,5 cm of residual tumor in the prostatectomy specimen after neoadjuvant therapy.
次要结局
- Rate of undetectable PSA(12 months)
- Rate of Grade ≥ 3 CTCAE adverse events(3 months)
- Residual cellularity rate(3 months)
- PSA decline rate(3 months)
- Rate of positive surgical margins(3 months)
- Pathologic downgrading(3 months)