Phase I Multiple Dose Pharmacokinetic Study of Lycopene Delivered in a Well-Defined Food-Based Lycopene Delivery System (Tomato Paste-Oil Mixture) in Patients at Increased Risk for Developing Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 主要终点
- Toxicity as measured by NCI CTC v2.0
研究概览
简要总结
RATIONALE: Chemoprevention is the use of certain drugs or substances to keep cancer from forming, growing, or coming back. The use of lycopene, a substance found in tomatoes, may keep prostate cancer from forming in patients at high risk of developing prostate cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of lycopene in preventing prostate cancer in patients who are at high risk of developing prostate cancer.
详细描述
OBJECTIVES:
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Define the toxicity and safety of lycopene administered as a food-based delivery system as a chemoprevention agent in patients who are at a high risk of developing prostate cancer.
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Define the pharmacokinetics and tissue distribution in patients receiving this regimen.
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Characterize surrogate endpoint biomarkers (SEBs) in the peripheral blood, buccal mucosa, and the prostate itself, which will provide evidence of biological activity relevant to a chemoprevention effect.
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Characterize the oxidative stress state of the individual by studies of DNA oxidation in the prostate and buccal mucosa, as well as DNA oxidation and lipid peroxidation within the peripheral blood.
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Define the effects of lycopene through a food delivery system on prostate histology (prostatic intraepithelial neoplasia), markers of cellular proliferation [PCNA], and apoptosis in the prostate.
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Evaluate the effects of lycopene on the serum levels of total prostate-specific antigen (PSA), free PSA, and PSA density.
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Provide the basic knowledge in reference to toxicity, pharmacokinetics, and SEBs needed to proceed to a large phase II or III lycopene study in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive oral lycopene in tomato paste and olive oil, once, twice, or three times daily for 3 months.
研究设计
- 研究类型
- Interventional
- 主要目的
- Prevention
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Elevated prostate-specific antigen (PSA), meeting 1 of the following criteria:
- •PSA > 4.0 ng/mL for patients at any age
- •PSA > 2.0 ng/mL for patients 35 to 49 years of age
- •PSA rise (velocity) of > 0.75 ng/mL over the past year
- •Has undergone a prostate biopsy* (following findings of elevated PSA) within the past 180 days that failed to reveal prostate cancer
- •Prostate intraepithelial neoplasia allowed NOTE: *At least 4 core biopsies are considered acceptable
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 80-100%
- •Bilirubin ≤ 2.0 mg/dL
- •AST and ALT ≤ 2 times upper limit of normal
- •Creatinine ≤ 2.0 mg/dL
- •WBC ≥ 3,000/mm^3
- •Hemoglobin ≥ 11.0 g/dL
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 125,000/mm^3
- •No history of gastrointestinal malabsorption or other condition affecting drug absorption
- •No history of food allergy to tomato-based products
- •No history of any chronic medical condition that, in the judgment of the investigator, may pose threat or additional risk to the patient (including a current history of alcohol or drug abuse)
- •No active history of cancer or other illnesses that, in the opinion of the investigator, could represent a threat to patient's life, including congestive heart failure or uncontrolled hypertension
- •PRIOR CONCURRENT THERAPY:
- •No participation in any other experimental trial within the past 4 weeks
- •No concurrent chronic use of nonsteroidal anti-inflammatory drugs
- •No concurrent participation in another experimental trial
- •No concurrent supplements (except multivitamins), including herbal and soy products
排除标准
- 未提供
结局指标
主要结局
Toxicity as measured by NCI CTC v2.0
Feasibility of daily consumption of prescribed volumes of the formulation
Tissue distribution of lycopene (oral mucosa and prostate tissue)
Serum lycopene levels, including other carotenoids and lipid soluble vitamins, at 1 and 3 months
Pharmacokinetics at 1 and 3 months
Modulation of surrogate endpoint biomarkers which include oxidative stress in blood, oral mucosa, and prostate tissue
Cellular proliferation as measured by proliferating cell nuclear antigen (PCNA)
Modulation of serum prostate-specific antigen
Apoptosis as measured by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling in prostate tissue
Serum levels of insulin-like growth factor (IGF-1) and the modulation of prostate histology (prostatic intraepithelial neoplasia [PIN], when and if present)
次要结局
未报告次要终点