Abiraterone Acetate Maintenance in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer. Randomized Phase II Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 119
- 试验地点
- 17
- 主要终点
- 1 year radiologic progression free survival
研究概览
简要总结
Prostate cancer is the most frequently diagnosed non-skin cancer, and the second leading cause of men cancer death in the United States. Hormonal therapy remains a first-line treatment for metastatic prostate cancer. Initial responses to hormonal therapy with chemical or surgical castration are quite favorable, however, most patients will progress to a castration-resistant phase of the disease. Docetaxel is the primary chemotherapeutic option for patients with mCRPC.
Abiraterone is a novel, selective, irreversible, and potent inhibitor of 17-[alpha]-hydroxylase/17,20-lyase (CYP17) enzymatic activity that has recently been demonstrated to further reduce testosterone levels in the blood to undetectable range (< 1 ng/dL) and is suggested to reduce de novo intratumor androgen synthesis. Abiraterone demonstrated activity in castration resistant prostate cancer patients previously treated with docetaxel chemotherapy. Recently, results of a phase III trial comparing abiraterone plus prednisone vs placebo plus prednisone in asymptomatic and without visceral metastasis, castration-resistant metastatic prostate cancer patients, demonstrated a better radiological progression free survival for abiraterone treated patients and a trend towards a better survival was clear for abiraterone treated patients.
No clinical evidence exists about efficacy of chemotherapy and antiandrogen therapy combination. All trials have been performed in patients in which LHRH agonist treatment was continued although there is not clear evidence about efficacy of hormonal treatment. Some retrospective studies suggest that androgen deprivation treatment should be maintained in chemotherapy treated patients. Abiraterone has been proved to suppress androgen levels to negative values, and to add efficacy to castration hormonal therapy. Combination of abiraterone with docetaxel chemotherapy seems promising adding efficacy to only docetaxel chemotherapy. A randomized phase II study comparing docetaxel + prednisone + abiraterone to docetaxel + prednisone in mCRPC in patients treated previously with abiraterone, seems promising to explore addition of efficacy to taxotere after abiraterone hormonal treatment.
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 written informed consent
- •Male aged 18 years and above
- •Histologically or cytologically confirmed adenocarcinoma of the prostate.
- •Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT, MRI.
- •Prostate cancer progression to previous castration treatment documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria or bone scan progression
- •Asymptomatic or mildly symptomatic from prostate cancer
- •Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM).
- •Previous anti-androgen therapy and progression after withdrawal.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Hemoglobin >= 10.0 g/dL independent of transfusion
- •Platelet count >= 100,000/µL
- •Serum albumin >= 3.5 g/dL
- •Serum creatinine < 1.5 x ULN or a calculated creatinine clearance >= 60 mL/min
- •Serum potassium >= 3.5 mmol/L
- •Liver function: a. Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert's disease) b. AST or ALT < 2.5 x ULN
- •Life expectancy of at least 6 months
- •Patients who have partners of childbearing potential must be willing to use a method of birth control
排除标准
- •Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
- •Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone daily.
- •Pathological finding consistent with small cell carcinoma of the prostate
- •Liver or visceral organ metastasis
- •Known brain metastasis
- •Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1
- •Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC
- •Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day
- •Radiation or radionuclide therapy for treatment of metastatic CRPC
- •Previously treated with ketoconazole for prostate cancer for greater than 7 days
- •Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
- •Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1
- •Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1
- •Uncontrolled hypertension (systolic BP >= 160 mmHg or diastolic BP >= 95 mmHg).
- •Active or symptomatic viral hepatitis or chronic liver disease
- •History of pituitary or adrenal dysfunction
- •Clinically significant heart disease
- •Atrial Fibrillation, or other cardiac arrhythmia requiring therapy
- •Other malignancy, except non-melanoma skin cancer, with a >= 30% probability of recurrence within 24 months
- •Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
- •Any condition which, in the opinion of the investigator, would preclude participation in this trial.
研究组 & 干预措施
Arm A
docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d
干预措施: docetaxel 75 mg/m2 + prednisone 10 mg/d + abiraterone 1000 mg/d (Drug)
Arm B
docetaxel 75 mg/m2 + prednisone 10 mg/d
干预措施: docetaxel 75 mg/m2 + prednisone 10 mg/d (Drug)
结局指标
主要结局
1 year radiologic progression free survival
时间窗: 1 year
Time from randomization to radiologic disease progression
次要结局
- Overall survival(Up to 3 years)
- Radiologic progression free survival(Up to 1 year)
- PSA progression free survival(Up to 3 weeks)
- PSA response rate(Up to 3 weeks)
- Objective response rate(Up to 12 weeks)
- Quality of life rate(Up to 12 weeks)
- Time to skeletal-related event(Up to 12 weeks)
- Time to opiate use for cancer pain(Up to 3 weeks)
- Time to pain progression(Up to 3 weeks)
- Safety profile(Up to 3 weeks)