Impact of Atorvastatin on Prostate Cancer Progression After Initiation of Androgen Deprivation Therapy - Lipid Metabolism as a Novel Biomarker to Predict Prostate Cancer Progression
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 10
- 主要终点
- Castration resistance
研究概览
简要总结
This randomized double-blind placebo-controlled trial tests whether intervention with atorvastatin delays development of castration resistance compared to placebo during androgen deprivation therapy (ADT) for prostate cancer.
详细描述
Cholesterol-lowering statin drugs have been reported to lower proliferation activity in prostate cancer, delay occurrence of castration resistance and reduce the risk of prostate cancer death. Therefore, it is important to test statins' efficacy in addition to conventional prostate cancer treatment in a randomized, placebo-controlled trial.
This phase 3 randomized double-blind placebo-controlled trial will explore whether intervention with atorvastatin delays prostate cancer progression i.e. development of castration resistance compared to placebo during androgen deprivation therapy (ADT) for metastatic or recurrent prostate cancer.
Secondary objectives include exploring whether atorvastatin lowers prostate cancer-specific or overall mortality compared to placebo, and to demonstrate whether changes in serum lipid parameters predict disease recurrence and occurrence of adverse genomic changes predicting castration resistance among prostate cancer patients during ADT.
The study recruitment target is 400 participants who start ADT as management of metastatic or recurrent prostate cancer. These men will be randomized 1:1 (200 + 200) to receive blinded study drug, either 80 mg of atorvastatin daily or placebo until disease recurrence i.e. development of castration resistance or for a maximum of five years.
The study will be carried out in collaboration between urological departments of University Hospitals in Finland as a project of the national FinnProstata study group, Herlev University Hospital in Denmark, Vestfold and Telemark hospitals in Norway and the Tartu University Hospital in Estonia.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histopathologically confirmed metastatic (radiologically confirmed bone or soft tissue metastasis or enlarged lymph nodes at minimum 15 mm in diameter beyond the pelvic lymph nodes) or recurrent (requiring treatment after curative-intent surgery or radiotherapy) adenocarcinoma of the prostate for which androgen deprivation or antiandrogen therapy (GnRH agonist/antagonist, bicalutamide/flutamide, surgical castration or enzalutamide/abiraterone monotherapy) is initiated as definitive treatment no longer than 3 months before recruitment
- •previous prostatectomy and radiation therapy allowed
- •ADT/antiandrogen therapy for neoadjuvant hormone therapy is not included
- •Willingness to participate and signing of informed consent
排除标准
- •Statin use at the time of recruitment or within 6 months of it
- •Previous adverse effects during statin therapy
- •Familial hypercholesterolemia or very high total cholesterol (9.3 mmol/l or above)
- •Clinically significant renal insufficiency (serum creatinine above 170 µmol/l) or liver insufficiency (serum alanine aminotransferase more than 2x above the upper limit of normal range)
- •Use of drugs that may interact with statins (St John's Wort, HIV protease inhibitors, ciclosporin, macrolide antibiotics, fucidic acid, phenytoin, carbamazepine, dronedarone or oral antifungal medication).
研究组 & 干预措施
Atorvastatin
Capsules of atorvastatin. Daily dose of 80 mg for max. 10 years or until development of castration resistance.
干预措施: Atorvastatin 80mg (Drug)
Placebo
Identical capsules as in the atorvastatin arm, but including no active ingredient. Used daily for max. 10 years or until development of castration resistance
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Castration resistance
时间窗: From date of randomization until the date of first occurrence of castration resistance, assessed up to 60 months
Castration resistance is defined as PSA progression (three consecutive PSA rises measured at least 1 week apart with two \> 50% increases over the nadir and PSA \> 2 ng/ml) or radiological disease progression (appearance of two or more lesions in bone scan or soft tissue enlargement as per RECIST criteria) with serum testosterone at castrate level (\< 1.73 nmol/l; 50 ng/dl) during ADT.
次要结局
- Lipid levels(From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months)
- Prostate cancer mortality(From date of randomization until the date of prostate cancer death, assessed up to 60 months)
- Overall survival(From date of randomization until the date of death due to any cause, assessed up to 60 months)
- Fasting blood glucose(From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months)
- Prostate cancer-specific quality of life (QOL)(From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 12 month intervals up to 60 months)
- Circulating cell-free DNA(At enrollment and at occurrence of castration resistance, assessed up to 60 months)
- Occurrence of cardiovascular events during ADT(From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months)
- General quality of life (QOL)(From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 12 month intervals up to 60 months)
研究者
Teemu Murtola
MD, PhD, professor
Tampere University Hospital