A Canadian Phase II, Placebo-controlled Randomized Trial of Bicalutamide in Patients Receiving Maintenance Avelumab for Metastatic Urothelial Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Rate of bladder tumor recurrence
研究概览
简要总结
This is a Phase II, multi-center, placebo-controlled randomized controlled trial of standard of care (SOC) avelumab versus SOC avelumab with bicalutamide for patients with metastatic or locally advanced urothelial carcinoma.
详细描述
Urothelial carcinoma (UC) is the second most common urological cancer after prostate cancer. Non-muscle invasive bladder cancer (NMIBC) is the most common form (~75%). Muscle-invasive bladder cancer (MIBC) is found at presentation in ~25% of patients, with 10-20% of NMIBC eventually becoming MIBC. Risk groups for NMIBC are based on number of tumours, stage and size. Almost half of patients with MIBC eventually progress to metastatic disease.
Treatments for metastatic urothelial carcinoma (mUC) have evolved rapidly over the last several years. Pembrolizumab demonstrated benefit as second line therapy for locally advanced and metastatic UC. Subsequently, the landmark Phase III randomized JAVELIN trial showed that the addition of avelumab as maintenance therapy following a response to chemotherapy for mUC significantly prolonged overall survival relative to best supportive care (hazard ratio (HR) = 0.69; 95% confidence interval (CI), 0.56-0.86; P = 0.001). Overall survival and progression-free survival were 21.4 months (18.9 to 26.1) and 5.5 (4.2 to 7.2) months, respectively. This trial established avelumab as the SOC treatment and initial immunotherapy for mUC following chemotherapy.
The investigators have selected a double-blind placebo-controlled randomized study design to be able to assess the pragmatic endpoint of investigator-assessed clinical progression. Randomization will assign patients 2:1 to bicalutamide 150mg daily plus SOC avelumab or placebo plus SOC avelumab. Patients will be followed every 3 months after avelumab treatment has started and until progression.
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 (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 or greater and able to provide informed consent for the trial;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening;
- •Patients with histologically confirmed urothelial carcinoma;
- •Patients is a candidate for a course of maintenance avelumab treatment for metastatic or locally advanced urothelial carcinoma;
- •Male patients with partners of child-bearing potential must agree to 2 acceptable forms of birth control and be continued for at least 130 days after study drug is discontinued.
排除标准
- •Patients with a history of liver disease whose hepatic enzymes, alkaline phosphatase or bilirubin are greater than twice the upper limit of normal will be ineligible.
- •Patients with neutrophils (< 1,000/μL) will be ineligible.
- •Patients on androgen replacement therapy, or those with prostate cancer or other diseases currently treated with systemic hormonal therapy will be ineligible for study enrollment. Patients receiving 5-alpha reductase inhibitors will not be excluded.
- •Patients who have a concurrent malignancy other than UC within the past years for which treatment is planned within the next 6 months.
- •Patients taking an investigational drug within 2 weeks of enrollment into this study.
- •Patients receiving or planning to receive coumadin therapy.
- •Female patients with childbearing potential are excluded due to known teratogenic effects of bicalutamide.
研究组 & 干预措施
Bicalutamide
standard of care (SOC) avelumab with 150mg daily oral bicalutamide
干预措施: Bicalutamide 150 mg (Drug)
Placebo
standard of care (SOC) avelumab with daily oral placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of bladder tumor recurrence
时间窗: 30 months
The primary outcome will be to the time to investigator-assessed progression on avelumab therapy.
次要结局
未报告次要终点