A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 主要终点
- Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions
研究概览
简要总结
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of ACAPHA, a combination of six herbs, may prevent lung cancer from forming in former smokers with bronchial intraepithelial neoplasia.
PURPOSE: This randomized phase II trial is studying the side effects and how well ACAPHA works in preventing lung cancer in former smokers with bronchial intraepithelial neoplasia.
详细描述
OBJECTIVES:
- Determine the efficacy and safety of multi-herbal agent ACAPHA in former smokers with bronchial intraepithelial neoplasia.
- Evaluate whether ACAPHA can modulate other surrogate endpoint biomarkers of aberrant methylation, cell cycle regulation, apoptosis, as well as phase I and II enzyme regulation.
- Establish a library of in vivo confocal microendoscopy images with corresponding histopathology, nuclear morphometry, and other biomarker information to assess the potential of confocal microendoscopy as a nonbiopsy method in assessing the effect of chemoprevention agents.
OUTLINE: Patients are stratified according to gender. Patients are randomized to 1 of 2 arms.
- Arm I: Patients receive oral multi-herbal agent ACAPHA twice daily for 6 months. Patients achieving a partial response receive an additional 6 months of ACAPHA.
- Arm II: Patients receive oral placebo twice daily for 6 months. Patients achieving a partial response receive an additional 6 months of placebo. Patients with progressive disease receive ACAPHA twice daily for 6 months.
Patients undergo sputum cytology, oral and bronchial brushings, bronchoalveolar lavage, and bronchial tissue biopsies at baseline and at 6 and 12 months. Samples are analyzed for histopathological and morphometric cell changes; MIB-1 bcl-2, and TUNEL immunostaining; methylation biomarkers; and gene expression analysis of RNA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •One or more areas of bronchial intraepithelial neoplasia (IEN) (metaplasia/dysplasia) with a nuclear morphometry index > 1.36 and a surface diameter > 1.2 mm on autofluorescence bronchoscopy
- •Atypical sputum cells as determined by computer-assisted image analysis
- •Former smoker (i.e., stopped smoking at least 1 year ago) who has smoked at least 30 pack-years (i.e., 1 pack/day for 30 years or more)
- •Exhaled carbon monoxide level < 5 ppm
- •No invasive cancer on bronchoscopy or abnormal spiral chest CT scan suspicious of lung cancer
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0 or 1
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Normal renal function tests (BUN, creatinine, urinalysis)
- •Normal liver function tests (AST, ALT, bilirubin, alkaline phosphatase)
- •No chronic active hepatitis or liver cirrhosis
- •No acute bronchitis or pneumonia within the past month
- •No known reaction to xylocaine
- •No medical condition that, in the opinion of the investigator, could jeopardize the patient's safety during participation in the study, including any of the following:
- •Acute or chronic respiratory failure
- •Unstable angina
- •Uncontrolled congestive heart failure
- •Bleeding disorder
- •PRIOR CONCURRENT THERAPY:
- •Not specified
排除标准
- 未提供
研究组 & 干预措施
ACAPHA
干预措施: multi-herbal agent ACAPHA (Dietary Supplement)
Sugar Pill
干预措施: Sugar Pill (Dietary Supplement)
结局指标
主要结局
Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions
时间窗: 12 months
次要结局
- Changes in the severity of dysplasia by bronchial biopsy(6 months)
- Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL)(12 months)
- MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies(12 months)
- Methylation biomarkers in the sputa, oral brush, and BAL cells(12 months)
- Gene expression analysis of RNA from bronchial brush cells(12 months)
- Volumetric measurement of CT scan-detected lung nodules before and after treatment(12 months)