A Randomized, Double Blind, Trial of Metformin and Atorvastatin in Delaying Androgen Deprivation Therapy Among Men With Rising PSA Following Radical Prostatectomy or Radiotherapy: The LIGAND (LIpitor and biGuanide to Androgen Delay) Trial
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy.
研究概览
简要总结
This study is a randomized trial examining the administration of a combination of biguanide metformin and atorvastatin ("Lipitor") to men who are experiencing rising prostate-specific antigen (PSA) levels, despite having undergone radical therapy (surgery and/or radiation).
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
- Triple (Participant, Care Provider, Investigator)
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
- •Willing and able to provide informed consent
- •Histologically confirmed adenocarcinoma of the prostate
- •History of radical therapy (i.e., radical prostatectomy, radiotherapy, brachytherapy or prostatectomy with salvage radiotherapy)
- •Serum testosterone levels 8.0 nmol/L (230 ng/dL) or greater
- •Not currently undergoing treatment for hyperlipidemia or diabetes mellitus
- •LDL-cholesterol levels 5 mmol/L or lower
- •HgA1c 6.5% or lower
- •PSA levels between 2 and 5 ng/mL
排除标准
- •Subjects that have been treated for prostate cancer with any of the following:
- •i. Cytotoxic chemotherapy; ii. Hormonal therapy within past 3 years; iii. Oral glucocorticoids; iv. Gonadotropin-releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin, degarelix)
- •Past treatment with the 5-α reductase inhibitors finasteride and dutasteride within past 5 years
- •Past treatment with drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
- •Use of metformin or statins within past 2 years
- •Planned or concurrent use of metformin, sulfonylureas, thiazolidinediones or insulin for any reason
- •Known hypersensitivity or intolerance to metformin or atorvastatin
- •Any clinically significant laboratory abnormalities (e.g., severe renal or hepatic impairment) which in the judgment of the investigator would affect the patient's health or the outcome of the trial
- •Any condition associated with increased risk of metformin-associated lactic acidosis (e.g., congestive heart failure defined as New York Heart Association (NYHA) class III or IV, history of any type of acidosis, habitual intake of 4 or more alcoholic beverages per day)
- •Abnormal liver function test
- •Abnormal organ and marrow function
研究组 & 干预措施
Metformin and Atorvastatin
Atorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
干预措施: Metformin (Drug)
Metformin and Atorvastatin
Atorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
干预措施: Atorvastatin (Drug)
Placebo
One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
干预措施: Placebo (corresponding to metformin) (Drug)
Placebo
One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
干预措施: Placebo (corresponding to atorvastatin) (Drug)
结局指标
主要结局
Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy.
时间窗: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
次要结局
- Time to disease progression(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Body mass index(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Time to androgen deprivation therapy(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Time to PSA progression(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Circulating glycated hemoglobin levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- C-peptide levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Adipokine levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- LDL/HDL cholesterol levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Triglyceride levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Incidence of adverse events during administration of metformin and atorvastatin to men with prostate cancer.(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)