Phase I Multiple Dose Study of 12-Week Treatment by Se-Methyl-L-Cysteine(MSC) and L SeMet in Adult Males
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 3
- 主要终点
- Clinical toxicity of Se-methyl-seleno-L-cysteine according to the NCI CTCAE version 4.0
研究概览
简要总结
This randomized phase I trial studies the side effects and the best dose of Se-methyl-seleno-L-cysteine or selenomethionine in preventing prostate cancer in healthy participants. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of Se-methyl-seleno-L-cysteine or selenomethionine, two different types of selenium compounds, may prevent prostate cancer from forming.
详细描述
PRIMARY OBJECTIVES:
I. To determine the individual toxicity profiles of Se-methyl-seleno-L-cysteine (methyl selenocysteine; MSC) and selenomethionine (SeMet) administered to cohorts of men daily for twelve weeks, with dose escalation with each successive cohort.
SECONDARY OBJECTIVES:
I. To measure the pharmacokinetics of selenium, according to form (MSC vs SeMet): MSC and SeMet impacts on plasma, albumin, and urinary concentrations of selenium over 48 hours on dosing days 1 and 84.
II. To evaluate the pharmacodynamics of selenium by form (MSC vs SeMet): plasma, albumin, and urinary Selenoprotein P (Sepp1) concentrations and glutathione peroxidase (GPx) activity over 48 hours on dosing days 1 and 84.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Total body weight between 50 and 115 kg (110 and 250 lbs)
- •Hemoglobin (Hgb) > 12 mg/dL
- •Platelet count > 100,000/μL
- •Absolute neutrophil count (ANC) > 1000/μL
- •Creatinine =< institutional upper limit of normal (ULN)
- •Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) < 2.0 x ULN
- •Total bilirubin =< ULN (participants with a higher level of bilirubin presumed due to familial metabolism will be considered on an individual basis)
- •Life expectancy greater than 3 years
- •Participants must agree to use adequate contraception (barrier method of birth control; abstinence) from time of screening until study completion (i.e., for at least 2 weeks after last dose of study drug)
- •Ability to understand and the willingness to sign a written informed consent document
- •Agree to refrain from use of selenium (Se) supplements (other than the 100 mcg dose common in multivitamins) or Se-containing drugs while on study between 30 days before study drug initiation and Day 84
排除标准
- •Not willing to remain at Roswell Park Cancer Institute (RPCI), and in follow up, as required
- •Presence of medical conditions which, in the opinion of the investigator, would place either the participant or the integrity of the data at risk
- •Serum creatinine > ULN, SGOT or SGPT >= 2.0 x ULN, or bilirubin > ULN
- •Treatment with an investigational drug within 30 days prior to the dose of study drug
- •Use of selenium [Se] supplements greater than the 100 mcg dose common in multivitamins between 30 days before study drug initiation and Day 84
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational agent (e.g., reaction to other Se supplements)
- •Participants who have donated 1 unit of blood within 30 days prior to the first dose of investigational agent
- •Eastern Cooperative Oncology Group (ECOG) performance status > 1
- •Diagnosed with cancer, other than non-melanoma skin cancer, in last 2 years
- •Under treatment for any cancer
- •Use of glucose-lowering agents or a condition that would make a fast from 10:00 pm the evening before until 11:00 am on days 1 and 84 hazardous
- •American Urological Association (AUA) total symptom score > 10 or any individual symptom score of greater than or equal to 4
- •Psychiatric illness which would prevent compliance with the intervention or would prevent the patient from providing informed consent
- •Medical conditions which in the opinion of the treating physician would make this protocol unreasonably hazardous for the participant
研究组 & 干预措施
Arm III (placebo)
Participants receive placebo PO on days 1-84.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (Se-methyl-seleno L-cysteine)
Participants receive Se-methyl-seleno L-cysteine on days 1-84.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (Se-methyl-seleno L-cysteine)
Participants receive Se-methyl-seleno L-cysteine on days 1-84.
干预措施: Pharmacological Study (Other)
Arm I (Se-methyl-seleno L-cysteine)
Participants receive Se-methyl-seleno L-cysteine on days 1-84.
干预措施: Methylselenocysteine (Drug)
Arm II (selenomethionine)
Participants receive selenomethionine PO on days 1-84.
干预措施: Selenium (Dietary Supplement)
Arm II (selenomethionine)
Participants receive selenomethionine PO on days 1-84.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (selenomethionine)
Participants receive selenomethionine PO on days 1-84.
干预措施: Pharmacological Study (Other)
Arm III (placebo)
Participants receive placebo PO on days 1-84.
干预措施: Placebo (Other)
Arm III (placebo)
Participants receive placebo PO on days 1-84.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Clinical toxicity of Se-methyl-seleno-L-cysteine according to the NCI CTCAE version 4.0
时间窗: Up to 112 days
The safety and tolerability data will be summarized using descriptive statistics, by cohort and for all cohorts combined compared to placebo. Reported adverse events will be looked at for possible differences, where appropriate, using graphical methods.
Clinical toxicity of Se-methyl-L-cysteine compared to selenium after multiple doses, according to the NCI CTCAE version 4.0
时间窗: Up to 112 days
The safety and tolerability data will be summarized using descriptive statistics, by cohort and for all cohorts combined compared to placebo. Reported adverse events will be looked at for possible differences, where appropriate, using graphical methods.
次要结局
- Characterization of the pharmacokinetics of Se in the forms Se-methyl-seleno-L-cysteine and selenium at multiple doses(At baseline, and at and .5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hrs after dosing on days 1 and between days 70 and 84)