Randomized Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Change From Baseline in Bronchial Dysplasia Index at 12 Months
研究概览
简要总结
This research study involves taking an experimental anti-cancer dietary supplement called Sulforaphane (SF) or a placebo (product without any supplement content) over a period of twelve months in order to determine if it is a useful dietary supplement for prevention of lung cancer in humans.
The main goals of this research study are:
- To learn about the effects of giving Sulforaphane (SF) to former smokers who are still at high risk of developing cancer due to their smoking history and whether or not their condition improves, stays the same or becomes worse after Sulforaphane (SF) is given.
- To learn whether Sulforaphane (SF) might reverse some of the lung cell changes associated with future development of lung cancer.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double Blind
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Man or woman 55-75 years of age.
- •Patients with normal endobronchial biopsy findings or pre-cancerous lesions at baseline will be eligible for the study. Pre-cancerous lesions include (a) reserve cell hyperplasia, (b) squamous metaplasia, (c) mild dysplasia, (d) moderate dysplasia, and (e) severe dysplasia.
- •A former smoker who has a history of smoking with ≥30 pack-years, quits smoking within the past 10 years, and has ≥1 year sustained abstinence from smoking.
- •Female subjects must be of non-child bearing potential or must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential.
- •Male and female subjects of childbearing potential must be willing to use adequate barrier methods of contraception from the time starting with the screening visit through 30 days after the last dose of study therapy.
- •Abstinence is acceptable if this is the established and preferred contraception for the subject.
- •Generally healthy with liver enzyme and blood count values within the ranges shown below on the blood sample drawn at the baseline screening visit. Specifically:
- •White blood cells ≥ 3,000/mL Total bilirubin ≤ 1.5 x ULN (upper limits of normal) AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN BUN and serum creatinine ≤ 1.5 x ULN Serum pregnancy test Negative
- •The presence of airflow obstruction on spirometry (GOLD II or greater, Forced Expiratory Volume in the first second (FEV1) <80%) Chronic Obstructive Pulmonary Disease (COPD); and/or any emphysema on CT scan.
- •Participants must have a Southwest Oncology Group (SWOG) performance status of 0-2
- •Participants must be able and willing to undergo a bronchoscopy before and after treatment for 12 months.
- •Patients must be fully informed of the investigational nature of this study and must sign an informed consent in accordance within institutional and regulatory guidelines.
排除标准
- •Carcinoma in situ or invasive cancer on baseline endobronchial biopsy.
- •A malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- •Severe lung disease or inability to undergo two bronchoscopies.
- •Had pneumonia or acute bronchitis for at least 2 weeks prior to enrollment.
- •Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or rare (< 2 minutes) premature ventricular contractions are not exclusionary.
- •Evidence of clinically active coronary artery disease, including myocardial infarction within 6 weeks, chest pain, or congestive heart failure, or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the study.
- •Hypoxemia (less than 90% saturation with supplemental oxygen).
- •Prior chemotherapy or thoracic radiation within the past 5 years.
- •Woman who is pregnant or plan to be pregnant in next 12 months, or is breast feeding or plan to begin breast feeding in next 12 months.
- •Life expectancy of < 12 months.
- •Have a history of irritable bowel disease such as Crohn's disease and ulcerative colitis.
研究组 & 干预措施
Sulforaphane (Study Drug)
Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane
干预措施: Sulforaphane (Dietary Supplement)
Placebo
Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Bronchial Dysplasia Index at 12 Months
时间窗: 12 months
To explore if daily oral dose of 120 micromole SF can modulate the changes in bronchial dysplasia from endoscopic biopsies in former smokers at high risk for lung cancer. All bronchial biopsies were formalin fixed, paraffin embedded, and H\&E stained for subsequent morphologic evaluation and classification defined by the World Health Organization The scale to score the biopsy: 1= normal; 2= reserve cell hyperplasia; 3 = squamous metaplasia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ; and 8 = invasive carcinoma. The higher the score the worse the possible outcome.
Cell Proliferation Marker Ki-67
时间窗: 12 months
The primary outcome focuses on the changes of bronchial dysplasia index with cell proliferation marker Ki-67. The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, cell proliferation marker Ki-67. Besides the inhibition of tumor incidence and multiplicity, the use of sulforaphane can inhibit cellular proliferation markers such as Ki-67 and induction of apoptosis hallmarks of tumorigenesis. Ki-67 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
Apoptosis Marker TUNEL
时间窗: 12 months
The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker TUNEL in bronchial biopsies in former smokers at high risk for lung cancer. TUNEL will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
Apoptosis Marker Caspase-3
时间窗: 12 months
The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker Caspase-3 in bronchial biopsies in former smokers at high risk for lung cancer. Caspase-3 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
次要结局
- Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples(12 Months)
- Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples(12 months)
- Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0(12 Months)
- Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples(12 months)
- Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples(12 months)
- Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples(12 months)
- Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples(12 months)
- Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples(12 months)
- Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples(12 months)
研究者
Jian-Min Yuan, MD
Principal Investigator
University of Pittsburgh