Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC-RP Trial): A Randomized, Open-label, Multi-centre Phase-2 Study Evaluating the Pathological Complete Response (pCR) Rate Following Neoadjuvant Therapy in Participants With High-risk Prostate Carcinoma for Whom Radical Prostatectomy is Indicated
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 5
- 主要终点
- Pathological complete response
研究概览
简要总结
This study evaluates the use of chemotherapy with cabazitaxel in addition to abiraterone acetate, prednisone, and leuprolide in neoadjuvant setting prior to radical prostatectomy in patients with high-risk prostate carcinoma. Half of the participants will receive treatment with abiraterone acetate, prednisone, leuprolide, and cabazitaxel, while the other half will receive only abiraterone acetate, prednisone, and leuprolide.
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
- None
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
- •Willing and able to provide informed consent;
- •Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with a minimum of 3 cores positive for tumour;
- •Tumour biopsy tissue accessible for downstream evaluation;
- •Must be candidates for radical prostatectomy and considered surgically resectable by urologic evaluation;
- •High Risk D'Amico score defined as either PSA > 20, Gleason score ≥ 8 as determined by the local pathologist; or T2c-3 based on DRE, pathologic review +/- imaging;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
- •No evidence of metastatic disease or nodal disease as determined by radionuclide bone scans and computed tomography (CT)/magnetic resonance imaging (MRI); non-pathological lymph nodes must be less than 15 mm in the short (transverse) axis;
- •Able to swallow the study drug(s) as prescribed and comply with study requirements;
- •Required initial laboratory values:
- •Absolute neutrophil count (ANC) ≥ 1500/μL;
- •Platelet count ≥ 100,000/μL;
- •Hemoglobin ≥ 90 g/L;
- •Creatinine ≤ 175 μmol/L;
- •Bilirubin ≤ upper limit of institutional normal (ULN);
- •AST/ALT ≤ 1.5 × ULN.
排除标准
- •Received an investigational agent within 4 weeks prior to screening;
- •Stage T4 prostate cancer by clinical examination or radiologic evaluation;
- •Hypogonadism or severe androgen deficiency as defined by screening serum testosterone below the normal range for the institution;
- •Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer;
- •Receiving concurrent androgens, estrogens, or progestational agents, or received any of these agents within the 6 months prior to randomization;
- •History of another malignancy within the previous 5 years other than curatively treated nonmelanomatous skin cancer and non-muscle invasive bladder cancer;
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiovascular disease, unstable angina pectoris, cardiac arrhythmia that is symptomatic or requires active therapy; deep venous thrombosis within 3 months prior to randomization;
- •Previous use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988);
- •Liver injury or disease (e.g., viral hepatitis, liver failure Child-Pugh Class C).
研究组 & 干预措施
Abiraterone acetate + prednisone + leuprolide + cabazitaxel
Participants randomized to this arm will receive abiraterone acetate (1000 mg/day), prednisone (5 mg twice daily), leuprolide (22.5 mg every 3 months), and cabazitaxel (20 mg/m2, with 6 mg pegfilgrastim administered 24 h following cabazitaxel) prior to radical prostatectomy.
干预措施: Abiraterone acetate with prednisone (Drug)
Abiraterone acetate + prednisone + leuprolide + cabazitaxel
Participants randomized to this arm will receive abiraterone acetate (1000 mg/day), prednisone (5 mg twice daily), leuprolide (22.5 mg every 3 months), and cabazitaxel (20 mg/m2, with 6 mg pegfilgrastim administered 24 h following cabazitaxel) prior to radical prostatectomy.
干预措施: Leuprolide (Drug)
Abiraterone acetate + prednisone + leuprolide + cabazitaxel
Participants randomized to this arm will receive abiraterone acetate (1000 mg/day), prednisone (5 mg twice daily), leuprolide (22.5 mg every 3 months), and cabazitaxel (20 mg/m2, with 6 mg pegfilgrastim administered 24 h following cabazitaxel) prior to radical prostatectomy.
干预措施: Cabazitaxel with peg-filgrastim (Drug)
Abiraterone acetate + prednisone + leuprolide
Participants randomized to this arm will receive abiraterone acetate (1000 mg/day) , prednisone (5 mg twice daily), and leuprolide (22.5 mg every 3 months) prior to radical prostatectomy.
干预措施: Abiraterone acetate with prednisone (Drug)
Abiraterone acetate + prednisone + leuprolide
Participants randomized to this arm will receive abiraterone acetate (1000 mg/day) , prednisone (5 mg twice daily), and leuprolide (22.5 mg every 3 months) prior to radical prostatectomy.
干预措施: Leuprolide (Drug)
结局指标
主要结局
Pathological complete response
时间窗: 24 weeks from start of treatment.
次要结局
- Pre-operative PSA levels(24 weeks of treatment)
- Mean nadir PSA levels(24 weeks of treatment)
- Percentage of participants achieving a PSA < 0.2 ng/mL(24 weeks of treatment)
- Percentage of participants achieving a 50 and 90% decrease in PSA levels(up to 24 weeks of treatment)
- Rate of positive surgical margins(up to 24 weeks of treatment)
- Rate of near-complete response (<5 mm tumour)(up to 24 weeks of treatment)
- Rate of extracapsular extension(up to 24 weeks of treatment)
- Rate of positive seminal vesicle involvement(up to 24 weeks of treatment)
- Severity of adverse events(Aup to 24 weeks of treatment)
- Rate of nodal involvement(up to 24 weeks of treatment)
- Tumour proliferation (Ki-67 index)(up to 24 weeks of treatment)
- Androgen receptor expression(up to 24 weeks of treatment)
- Incidence of adverse events(up to 24 weeks of treatment)
- Androgen levels (if optional biopsy tissue is available)(up to 24 weeks of treatment)
- Genomic alterations between pre- and post-treatment tissue(up to 24 weeks of treatment)