An Open Label, Randomized, Phase II Trial of Metabolic Complications in Patients Treated With Enzalutamide vs Standard ADT for the Treatment of Hormone Sensitive Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Metabolic Syndrome Incidence, Summarized by the Number of Patients With at Least 3 of the 5 Pre-specified Criteria
研究概览
简要总结
This randomized phase II trial compares enzalutamide with standard androgen deprivation therapy in reducing incidence of metabolic syndrome in patients with prostate cancer that has spread to other places in the body. Metabolic syndrome is defined as changes in cholesterol, blood pressure, circulating sugar levels, and body weight. Previous studies have shown that patients with prostate cancer, who have been treated with standard medical therapy that lowers testosterone levels, have an increased risk of these changes. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells instead of lowering testosterone levels. It is not yet known whether prostate cancer patients who receive enzalutamide will have reduced incidence of metabolic syndrome than patients who receive standard androgen deprivation therapy.
详细描述
PRIMARY OBJECTIVES:
I. To determine the incidence of metabolic syndrome within 12 months, as defined by the Adult Treatment Panel III, in patients treated with enzalutamide compared to standard androgen deprivation therapy.
SECONDARY OBJECTIVES:
I. To determine the incidence of metabolic syndrome within 6 months, as defined by the Adult Treatment Panel III, in patients treated with enzalutamide compared to standard androgen deprivation therapy.
II. To assess bone health, as measured by a dual-energy x-ray absorptiometry (DXA) scanner.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically proven adenocarcinoma of the prostate; if pathology is unavailable, the principal investigator (PI) may also make a determination of prostate cancer based on unequivocal clinic data
- •Patients with advanced prostate cancer suitable for systemic treatment defined as: having metastatic disease, a biochemical relapse after primary therapy, or patients in whom primary therapy is not appropriate or feasible; patients without metastatic disease will need evaluation for local therapy and deemed inappropriate or have refused this treatment option
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •Age > 18 years
- •Must use a condom if having sex with a pregnant woman
- •A male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration
- •Life expectancy estimated at > 12 months
- •Ability to understand and willingness to provide written informed consent document
排除标准
- •A history of androgen deprivation therapy; patients receiving hormonal therapy in the adjuvant and/or neoadjuvant setting must have discontinued therapy at least 6 months prior to day 1 of treatment AND have a serum testosterone level >= 50 ng/dL AND cannot have received more than 18 months of previous ADT
- •A history of orchiectomy
- •Previous androgen blockade (e.g. antiandrogens) in the last 3 months
- •Patients already meeting the criteria for metabolic syndrome as defined by the Adult Treatment Panel III Criteria which requires 3/5 parameters encompassing glucose control, blood pressure, lipids and waist circumference; patients with 2 of the parameters at baseline will be allowed enrollment provided that one of those risk factors is hypertension (>= 130/>= 85 mm Hg)
- •Baseline hypogonadism as defined as a testosterone < 50 ng/dL
- •PSA < 0.5 ng/dL
- •Serum vitamin D 25, hydroxy (OH) < 12 ng/mL
- •Active hepatitis C virus
- •Use of corticosteroids as defined by a daily dose of prednisone (or equivalent) of 5 mg or greater for more than 1 month continuously within 3 months of screening
- •Corrected calcium > 10.6 mg/dL
- •Absolute neutrophil count < 1500/uL
- •Platelet count < 100,000/uL
- •Hemoglobin < 9 g/dL
- •Total bilirubin >= 1.5 x upper limit of normal (ULN) (unless documented Gilbert's)
- •Alanine aminotransferase or aspartate aminotransferase >= 2.5 x ULN
- •Creatinine > 2 mg/dL
- •Clinically significant cardiovascular disease as evidenced by: myocardial infarction within 6 months of screening; uncontrolled angina within 3 months of screening; New York Heart Association (NYHA) class 3 or 4 congestive heart failure; clinically significant ventricular arrhythmia; Mobitz II/2nd degree/or 3rd degree heart block without a pacemaker in place; uncontrolled hypertension (HTN) (systolic > 180 mmHg or diastolic > 105 mmHg at screening)
- •Previous exposure to enzalutamide
- •Use of an investigational therapeutic within 30 days
- •History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agent
- •Known or suspected brain metastasis or active leptomeningeal disease
- •History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit
- •Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
研究组 & 干预措施
Arm I (enzalutamide)
Patients receive enzalutamide PO QD for 12 months in the absence of disease progression or unacceptable toxicity.
干预措施: Enzalutamide (Drug)
Arm II (ADT)
Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix SC or IM for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.
干预措施: leuprolide acetate (Drug)
Arm II (ADT)
Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix SC or IM for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.
干预措施: goserelin acetate (Drug)
Arm II (ADT)
Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix SC or IM for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.
干预措施: histrelin acetate (Drug)
Arm II (ADT)
Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix SC or IM for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.
干预措施: triptorelin (Drug)
Arm II (ADT)
Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix SC or IM for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.
干预措施: degarelix (Drug)
结局指标
主要结局
Metabolic Syndrome Incidence, Summarized by the Number of Patients With at Least 3 of the 5 Pre-specified Criteria
时间窗: Within the first 12 months of therapy
Metabolic syndrome will be assessed at the beginning of each course and defined by the presence of 3 of the following five traits: abdominal obesity, defined as a waist circumference \> 102 cm (\> 40 in); serum triglycerides \>= 150 mg/dL (1.7 mmol/L) or drug treatment for elevated triglycerides; serum high density lipoprotein (HDL) cholesterol \< 40 mg/dL (1 mmol/L) or drug treatment for low HDL; blood pressure \>= 130/\>= 85 mmHg or drug treatment for elevated blood pressure; and fasting plasma glucose (FPG) \>= 100 mg/dL (5.6 mmol/L) or drug treatment for elevated blood glucose.
次要结局
- Change in Free Fat Mass, as Measured by a DXA Scanner(Baseline to up to 12 months)
- Number of Patients With PSA Progression(Time from randomization to the earliest objective evidence of PSA progression as defined per protocol, assessed up to 30 days after the last dose of study drug)
- Change in Bone Turnover Markers, as Measured by Bone-specific Alkaline Phosphatase(Baseline and month 12)
- Change in Markers of Inflammation, as Measured by Circulating Hs-CRP(Difference between baseline and 12 months.)
- Change in Bone Turnover Markers as Measured by N-telopeptide(Baseline and 12 months)
- Metabolic Syndrome Incidence, Summarized by the Proportion of Patients With at Least 3 of the 5 Pre-specified Criteria(Within the first 6 months of therapy)
- Change in Fat Mass, as Measured by a DXA Scanner(Baseline to up to 12 months)
- Incidence of Adverse Events, Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.1(Up to 30 days after the last dose of study drug)
- Change in Bone Density(Baseline to 12 months)
- Change in Quality of Life (QOL) Scores, as Measured by the Functional Assessment of Cancer Therapy - Prostate (FACT-P) and Sexual Health in Men (SHIM)(Baseline to up to 7 months)
- Time to Radiographic Progression(Time from randomization to the earliest objective evidence of radiographic progression as defined per protocol, assessed up to 30 days after the last dose of study drug)
- Change in Physical Function, as Measured by Short Physical Performance Battery (SPPB).(Difference between baseline and 12 months.)