This phase II trial tests whether broccoli seed and sprout extract works to break down cancer causing substances of tobacco in heavy smokers. Smokers are at increased risk for developing lung, head and neck, and other cancers. Broccoli seed and sprout extract may help break down and remove toxic substances caused by tobacco use and possibly produce substances that may protect cells from tobacco smoke-induced damage in current smokers.
PRIMARY OBJECTIVE: I. To determine whether broccoli sprout/broccoli seed extract supplement (broccoli seed and sprout extract \[BSSE\]) sustainably increases the urinary excretion of the mercapturic acids of the tobacco carcinogens benzene and/or acrolein over a 12-week exposure period in otherwise healthy, current smokers. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of BSSE over a 12-week exposure period. II. To evaluate whether BSSE sustainably increases the urinary excretion of the mercapturic acid of the tobacco carcinogen crotonaldehyde. III. To evaluate the bioavailability of BSSE measured as sulforaphane (SF) metabolites and assess for a dose-response relationship between the effective SF dose delivered by BSSE and the detoxification of benzene and acrolein. IV. To determine whether the GSTM1 and GSTT1 genotypes are important genetic modulators of detoxification of tobacco carcinogens in the setting of prolonged exposure to BSSE. EXPLORATORY OBJECTIVES: I. To evaluate modulation of mucosal signatures of nuclear factor-erythroid factor 2-related factor 2 (NRF2) activation, inflammation, and innate immunity. II. To evaluate modulation of nasal epithelial gene signatures including smoking, lung cancer, and squamous dysplasia. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive broccoli seed and sprout extract orally (PO) once daily (QD) for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood, nasal epithelial cell, and buccal cell samples throughout the study. GROUP II: Patients receive placebo PO QD for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood, nasal epithelial cell, and buccal cell samples throughout the study. After completion of study, patients are followed up at 2-4 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
135
Undergo collection of blood, buccal cell, and nasal epithelial cell samples
Given PO
Given PO
Ancillary studies
University of Arizona Cancer Center - Prevention Research Clinic
Tucson, Arizona, United States
RECRUITINGGeorge Washington University Medical Center
Washington D.C., District of Columbia, United States
RECRUITINGRoswell Park Cancer Institute
Buffalo, New York, United States
RECRUITINGDetoxification of benzene and acrolein
Measured by changes in the urinary levels of their respective mercapturic acids, SPMA and 3-HPMA, from baseline.
Time frame: At baseline and 2, 4, 8, and 12 weeks
Incidence of adverse events (AE)s
Measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 5. The frequency and associated percentage of each specific AE will be tabulated by the treatment group and then compared via Fisher's exact test. The tolerability will be measured by the adherence rate and will be compared between the broccoli seed and sprout extract (BSSE) and placebo groups via Fisher's exact test.
Time frame: Up to 12 weeks
Increases in detoxification of crotonaldehyde
Will determine whether BSSE sustainably increases the detoxification of crotonaldehyde, as measured by changes in the creatinine-normalized urinary levels of its mercapturic acid metabolite, 3-HMPMA, over time. Similar to the carcinogens, benzene and acrolein, the detoxification of crotonaldehyde will be measured by change at 2 weeks, 4 weeks, 8 weeks and 12 weeks in the urinary excretion of 3-HMPMA from baseline, and a linear mixed effects model will be fit to changes in log-transformed urinary 3-HMPMA levels from baseline.
Time frame: At baseline and 2, 4, 8, and 12 weeks
Bioavailability of BSSE
Measured by urinary sulforaphane (SF) metabolites.
Time frame: At baseline and 2, 4, 8, and 12 weeks
Dose-response relationship between effective SF dose and the detoxification of benzene and acrolein
A dose-response relationship between SF metabolites and detoxification of benzene and/or acrolein will be assessed by a linear mixed effects model with random intercepts, in which changes from baseline in each of the log-transformed urinary mercapturic acid levels as the dependent variable (response) and changes from baseline in SF metabolites as the independent variable (dose).
Time frame: Baseline up to 12 weeks
Genetic modulators of detoxification of tobacco carcinogens
Will assess whether the GSTM1 and GSTT1 genotypes are important genetic modulators of detoxification of tobacco carcinogens in the setting of prolonged exposure to BSSE. The association of GSTM1 and GSTT1 genotypes with detoxification of benzene and/or acrolein will be assessed by a linear mixed effects model with random intercepts for changes from baseline in each of the log transformed mercapturic acid levels, in which the fixed effects include BSSE, genotype and time indicators and two-way and three-way interactions of BSSE, genotype and time indicators. This will allow us to study whether 1) the BSSE effect if significant is modulated by the genotypes, 2) the time effect if significant is modulated by the genotypes, or 3) the interaction effect between BSSE and time if significant is modulated by the genotypes.
Time frame: Up to 12 weeks
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