Phase IIA Trial of Curcumin Among Patients With Prevalent Subclinical Neoplastic Lesions (Aberrant Crypt Foci)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)
研究概览
简要总结
Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. Curcumin is a compound found in plants that may prevent colon cancer from forming. This phase II trial is studying how well curcumin works in preventing colon cancer in smokers with aberrant crypt foci.
详细描述
PRIMARY OBJECTIVES:
I. To determine mean percentage change from baseline in prostaglandin E2 (PGE2) within ACF pre and post 30 days of curcumin administration at a specified dose.
SECONDARY OBJECTIVS:
I. To determine mean percentage change from baseline in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF pre and post 30 days of curcumin administration at a specified dose.
II. To determine mean percentage change from baseline in PGE2 and 5-HETE within comparison normal mucosa pre and post 30 days of curcumin administration at a specified dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Current smoker with > 3 pack-year total smoking history
- •Subjects taking NSAIDS or ASA < 10 days month are eligible but must undergo 14 day washout and refrain from use during the study
- •Subjects who are:
- •Having a clinically indicated screening/surveillance colonoscopy (e.g. due to risk factors, personal history, or symptoms) OR
- •Not having a colonoscopy but are otherwise eligible. These subjects would undergo a flexible sigmoidoscopy.
- •ECOG performance status 0-2 (Karnofsky > 60%)
- •No severe organ dysfunction which might increase bleeding risk:
- •Demonstrated by: Normal hematologic status (WBC > 3,000/mm^3, hemoglobin > 10.0 gm/dl, and platelet-count >100,000/mm^3), normal hepatic function (bilirubin < 1.5 mg/dl, transaminases < 1.5x institutional norms), and normal renal function (serum creatinine < 2.0 mg/dl, documented in clinical chart 28 days prior to enrollment
- •Healthy current smokers (1 cigarette in previous yr) with > 3-pack year of cigarette smoking and able to provide written informed consent; there are no gender restrictions
- •The effects of curcumin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •NSAID or ASA use > 10 days /month; any current glucocorticoid use or omega 3-fatty acid supplement use
- •Evidence of the following chronic medical conditions such as:
- •Pregnant or lactating women and/or women who are contemplating pregnancy during the duration of the protocol
- •History of chronic inflammatory bowel disease or prior pelvic irradiation
- •History of peptic ulcer disease (PUD) endoscopically confirmed < 5 yrs from enrollment date
- •Newly diagnosed colorectal cancer or advanced adenoma < 1 yr from enrollment
- •Unspecified history of bleeding or coagulation disorder reported by patient or in medical history
- •Hereditary Colon Cancer syndromes (FAP or HNPCC)
- •Participants may not be receiving any other investigational agents
- •History of contact dermatitis from turmeric
- •Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because curcumin is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with curcumin, breastfeeding should be discontinued if the mother is treated with curcumin
研究组 & 干预措施
2g (curcumin)
Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
干预措施: laboratory biomarker analysis (Other)
2g (curcumin)
Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
干预措施: pharmacological study (Other)
2g (curcumin)
Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
干预措施: curcumin (Drug)
4g (curcumin)
Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
干预措施: laboratory biomarker analysis (Other)
4g (curcumin)
Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
干预措施: pharmacological study (Other)
4g (curcumin)
Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
干预措施: curcumin (Drug)
结局指标
主要结局
Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)
时间窗: At 30 day
Post-treatment prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue
Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)
时间窗: Baseline
Baseline prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue
次要结局
- Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third(At 30 day)
- Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third(At 30 day)
- Baseline Curcumin Concentration in Rectal Mucosa(Baseline)
- Post-treatment Curcumin Concentration in Rectal Mucosa(At 30 day)
- Post-treatment Curcumin Plasma Concentrations(At 30 day)
- Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa(Baseline)
- Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa(At 30 day)
- Change in Cyclooxygenases (COX-1, COX-2), and Lipoxygenase (5-LOX) Protein Abundance(Baseline to 30 days)
- Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)(Baseline)
- Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)(At 30 Day)
- Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa(Baseline)
- Changes in Total Aberrant Crypt Foci (ACF) Number(Baseline to 30 days)
- Baseline Curcumin Plasma Concentrations(Baseline)
- Baseline Curcumin Conjugates Concentration in Rectal Mucosa(Baseline)
- Post-treatment Curcumin Conjugates Concentration in Rectal Mucosa(At 30 day)
- Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa(At 30 day)
- Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third(At 30 day)
- Post-treatment Curcumin Conjugates Plasma Concentrations(At 30 day)
- Number of Participants at Each Adverse Event Grade Level(Baseline to 30 days)
- Baseline Curcumin Conjugates Plasma Concentrations(Baseline)