Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

Conditions
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Lung Cancer

Intervention / Treatment
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* Dietary Supplement: Sulforaphane
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulforaphane (Study Drug)<br>Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane | Dietary Supplement: Sulforaphane<br>* Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables.<br>* Other names: Avmacol®;|
| Placebo Comparator: Placebo<br>Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner | Drug: Placebo<br>* Inactive ingredients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchial dysplasia index | 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. | 12 months | 
| Cell proliferation marker Ki-67 | To explore if daily oral dose of 120 micromole SF can inhibit level of cell proliferation marker Ki-67 in bronchial biopsies of former smokers at high risk for lung cancer. | 12 months | 
| Apoptosis markers including caspase-3 and TUNEL | To explore if daily oral dose of 120 micromole SF can induce apoptosis markers caspase-3 and TUNEL in bronchial biopsies in former smokers at high risk for lung cancer. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene Expression | To explore if daily oral dose of 120 micromole SF can modulate the changes of the lung cancer-related gene expression markers in bronchial epithelia in former smokers at high risk for lung cancer. | 12 Months | 
| Bronchial Pre-malignant lesions | To explore if daily oral dose of 120 micromole SF can modulate the changes of bronchial premalignant lesions-related gene expression markers in former smokers at high risk for lung cancer. | 12 months | 
| Gene Expression Nasal Epithelia | To explore if daily oral dose of 120 micromole SF can modulate the similar changes of the gene expression markers in nasal epithelia. | 12 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | To determine the safety and toxicity of daily oral dose of 120 micromole SF in former smokers at high risk for lung cancer by monitoring and recording any potential SF-related adverse events (both expected and unexpected events). | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sulforaphane, Chemoprevention, Former Smokers