Phase II Randomized, Double Blind, Placebo-Controlled Trial of Broccoli Seed and Sprout Extract (BSSE), Avmacol ES, to Evaluate Sustained Detoxification of Tobacco Carcinogens in Heavy Smokers

PRIMARY OBJECTIVE:

1. 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:

1. To evaluate the safety and tolerability of BSSE over a 12-week exposure period.
2. To evaluate whether BSSE sustainably increases the urinary excretion of the mercapturic acid of the tobacco carcinogen crotonaldehyde.
3. 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.
4. 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:

1. To evaluate modulation of mucosal signatures of nuclear factor-erythroid factor 2-related factor 2 (NRF2) activation, inflammation, and innate immunity.
2. To evaluate modulation of nasal epithelial gene signatures including smoking, lung cancer, and squamous dysplasia.

Inclusion Criteria:

• Male or female current tobacco smokers with >= 20 pack years of self-reported smoking exposure and a current average use of >= 10 cigarettes/day
• Age >= 18 years
• Karnofsky performance scale >= 70%
• Absolute neutrophil count >= 1,000/microliter
• Platelets >= 100,000/microliter
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN
• Creatinine =< 1.5 x ULN
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• The effects of BSSE on the developing human fetus at the recommended therapeutic dose are unknown. For this reason,, women of child-bearing 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

Exclusion Criteria:

• History of invasive cancer within the past 2 years, except for excised and cured non-melanoma skin cancer or carcinoma in situ of the cervix. Participants who continue adjuvant treatment for an index cancer occurring > 2 years ago, such as adjuvant hormonal therapy for breast cancer, are excluded. Participants who are on anti-neoplastic treatment for a chronic malignancy, such as multiple myeloma or chronic myelogenous leukemia, are excluded
• Chronic, current or recent (within the past 2 weeks) use of systemic steroid doses equivalent to prednisone > 5 mg daily for continued use > 14 days. Use of inhaled steroids, nasal sprays, and topical creams for small body areas (< 10% body surface area) is allowed
• Participants may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Avmacol ES (BSSE)
• Uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• Pregnant or lactating women. Pregnant women are excluded from this study because the effects of BSSE on the developing human fetus are unknown. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with BSSE, Breastfeeding should be discontinued if the mother is treated with BSSE