Phase II Trial Targeting Gut Bacterial Androgen Production to Reverse Therapeutic Resistance to Abiraterone in Patients With Metastatic Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Number of participants with PSA30 response
研究概览
简要总结
To determine if dexamethasone or dexamethasone plus metronidazole restore sensitivity to abiraterone for the treatment of metastatic prostate cancer.
详细描述
To test whether giving dexamethasone with or without metronidazole in combination with abiraterone could help reverse resistance to abiraterone for patients with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone and prednisone (AA/P) is a second-line therapy for mCRPC given when first-line androgen deprivation therapy fails. However, resistance to AA/P can develop. The investigators do not know exactly how cancer becomes resistant, but there is evidence that suggests it could be due to androgen production by the bacteria in your gut (gut microbiome). This study is focused on the gut microbiome as a source of androgen production that could cause AA/P resistance in mCRPC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Males aged 18 years of age and above.
- •Prostate adenocarcinoma
- •Absolute PSA ≥ 2.0 ng/mL at screening.
- •PSA (+/- radiographic) progression after having been on abiraterone and prednisone for at least 12 weeks.
- •Must be maintained on a GnRH analogue or have undergone orchiectomy.
- •Participants must have a life expectancy ≥ 6 months
- •Ability to swallow study medication tablets
- •Willing to abstain from alcohol during and for 14 days after treatment with metronidazole
- •Willing and able to collect urine and stool samples per protocol
排除标准
- •Active infection or other medical condition that would make dexamethasone use contraindicated
- •Any chronic medical condition requiring a higher systemic dose of corticosteroid
- •Pathological finding consistent with small cell carcinoma of the prostate
- •Has imminent or established spinal cord compression based on clinical findings and/or MRI.
- •Chronic liver disease with Child-Pugh class C cirrhosis (see calculator in protocol)
- •Bilirubin >3x ULN or AST and ALT >5x ULN
- •Congenital prolonged QTc syndrome or QTc > 500 msec (non-paced rhythm)
- •History of pituitary or adrenal dysfunction
- •Uncontrolled diabetes (Hemoglobin A1c > 10%) or increasing doses of insulin within the past 4 weeks due to poorly controlled glucoses.
- •Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational drug study
- •Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:
- •Any uncontrolled major infection.
- •Crohn's disease or ulcerative colitis.
- •Known or suspected toxic megacolon and/or known small bowel ileus.
- •Known allergy to any of the compounds under investigation.
- •On antibacterial therapy within 30 days prior to administration of study treatment.
- •Any condition or situation which, in the opinion of the investigator, would put the subject at risk, or interfere with the subject's participation in this study.
研究组 & 干预措施
Arm 1: Abiraterone + Dexamethasone
Abiraterone acetate plus dexamethasone
干预措施: Dexamethasone (Drug)
Arm 1: Abiraterone + Dexamethasone
Abiraterone acetate plus dexamethasone
干预措施: Abiraterone acetate (Drug)
Arm 2: Abiraterone + Dexamethasone + metronidazole
Abiraterone acetate plus dexamethasone plus metronidazole
干预措施: Dexamethasone (Drug)
Arm 2: Abiraterone + Dexamethasone + metronidazole
Abiraterone acetate plus dexamethasone plus metronidazole
干预措施: Metronidazole (Drug)
Arm 2: Abiraterone + Dexamethasone + metronidazole
Abiraterone acetate plus dexamethasone plus metronidazole
干预措施: Abiraterone acetate (Drug)
结局指标
主要结局
Number of participants with PSA30 response
时间窗: 24 weeks
Number of participants with castration resistant prostate cancer who have a ≥ 30% decline in PSA from baseline until 24 weeks.
次要结局
- Number of participants with PSA50 response(12 weeks)
- PSA Progression Free Survival(12 weeks)
- Number of participants with progression(24 weeks)
- Number of grade 3-5 toxicities(24 weeks)