Broccoli Sprout/Broccoli Seed Extract Supplement in Decreasing Toxicity in Heavy Smokers

PRIMARY OBJECTIVES:

I. To determine whether broccoli sprout/broccoli seed extract supplement (Avmacol) increases
the urinary excretion of the mercapturic acid of the tobacco carcinogen, benzene, in healthy
volunteers who are current heavy smokers.

SECONDARY OBJECTIVES:

I. To determine whether Avmacol increases the urinary excretion of the mercapturic acids of
other tobacco carcinogens, including acrolein and crotonaldehyde.

II. To determine whether Avmacol increases the urinary excretion of the mercapturic acids of
tobacco carcinogens, normalized by bio-measurement of tobacco exposure.

III. To determine whether Avmacol upregulates the NRF2 target gene transcripts in the buccal
cells of current smokers.

IV. To evaluate for a dose-response relationship between Avmacol and the detoxification of
tobacco carcinogens and the expression of NRF2 target gene transcripts.

V. To determine the relationship between systemic study agent exposure and biomarker
modulation.

EXPLORATORY OBJECTIVES:

I. To determine whether the GSTM1 and GSTT1 genotypes are important genetic modulators of
detoxification of tobacco carcinogens with Avmacol treatment.

II. To bank specimens for future research including evaluation of tobacco gene signatures in
buccal and nasal epithelium and buccal cell nuclear morphometry.

OUTLINE: Participants are randomized into 1 of 2 arms.

ARM I: Participants receive lower dose broccoli sprout/broccoli seed extract supplement
orally (PO) daily for 10-14 days. After 10-14 days, participants receive higher dose broccoli
sprout/broccoli seed extract supplement PO daily for 10-14 days.

ARM II: Participants receive higher dose broccoli sprout/broccoli seed extract supplement PO
daily for 10-14 days. After 10-14 days, participants receive lower dose broccoli
sprout/broccoli seed extract supplement PO daily for 10-14 days.

After completion of study, participants are followed up at 10-14 days.

Inclusion Criteria:

- Current tobacco smokers with >= 20 pack years of self-reported smoking exposure and a
current average use of >= 10 cigarettes/day

- Karnofsky performance scale >= 70%

- Leukocytes >= 3,000/microliter

- Absolute neutrophil count >= 1,500/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])
=< 1.5 x ULN

- Creatinine =< ULN

- Fertile subjects must use adequate contraception (abstinence, barrier methods, or
birth control pills) prior to study entry and for the duration of study participation;
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, with the exception of excised and
cured non-melanoma skin cancer or carcinoma in situ of the cervix

- 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 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

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant or lactating women