Cigarette Smoking-Related Carcinoma, Tobacco-Related Carcinoma
Conditions
Brief summary
This randomized early phase I trial studies how well broccoli sprout/broccoli seed extract supplement works in decreasing toxicity in heavy smokers. Broccoli sprout/broccoli seed extract supplement is a dietary supplement made from broccoli sprout and seed extract powder, and may break down some of the cancer causing substances in tobacco smoke and produce substances that may protect cells from tobacco smoke-induced damage in current smokers.
Detailed description
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.
Interventions
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol | Baseline up to 14 days post intervention | Change in the overnight urinary excretion the mercapturic acid of benzene following 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline. |
| Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol | Baseline up to 14 days post intervention | Change in the overnight urinary excretion the mercapturic acid of benzene following 4 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the NRF2 Target Gene Transcripts | Baseline up to 14 days post intervention | Change in the expression of NQO1 in the buccal cells after 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of the gene expression of NQO1 between post intervention and baseline. |
| Systemic Study Agent Exposure | Up to 14 days post intervention | Change in the total urinary levels of sulforaphane and its glutathione-derived metabolites (i.e., the sum of the molar concentrations of sulforaphane and its glutathione-derived metabolites in urine). Data presented as ratio of the geometric mean of the total urinary levels of sulforaphane and its metabolites between post intervention and baseline. |
| Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens | Up to 14 days post intervention | Dose-response relationship between the Avmacol dose and the detoxification of tobacco carcinogens. Data presented as ratio of percent change of the overnight urinary excretion of mercapturic acid of benzene/acrolein/crotonaldehyde between the 8 tables and 4 tables dose. |
| Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde | Baseline up to 14 days post intervention | Change following 4 tablets per day and 8 tablets per day of Avmacol wad determined separately. Data presented as ratio of the geometric mean of overnight urinary excretion of the mercapturic acid of acrolein/crotonaldehyde between post intervention and baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| GSTM1 and GSTT1 Genotypes | Up to 14 days post intervention | Change in the urinary excretion of the mercapturic acids of tobacco carcinogens by GSTM1 and GSTT1 genotype. Data presented as ratio of the geometric mean of urinary excretion of mercapturic acid of benzene between post intervention and baseline for each genotype. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Avmacol Participants who initiated Avmacol intervention | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Avmacol |
|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 48 |
| other Total, other adverse events | 26 / 49 | 14 / 48 |
| serious Total, serious adverse events | 1 / 49 | 0 / 48 |
Outcome results
Primary
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol
Change in the overnight urinary excretion the mercapturic acid of benzene following 4 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline.
Time frame: Baseline up to 14 days post intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avmacol | Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol | 1.16 data presented as ratio; no unit |
Primary
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol
Change in the overnight urinary excretion the mercapturic acid of benzene following 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline.
Time frame: Baseline up to 14 days post intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avmacol | Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol | 1.19 data presented as ratio; no unit |
Secondary
Change in the NRF2 Target Gene Transcripts
Change in the expression of NQO1 in the buccal cells after 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of the gene expression of NQO1 between post intervention and baseline.
Time frame: Baseline up to 14 days post intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avmacol | Change in the NRF2 Target Gene Transcripts | 1.00 data presented as ratio; no unit |
Secondary
Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde
Change following 4 tablets per day and 8 tablets per day of Avmacol wad determined separately. Data presented as ratio of the geometric mean of overnight urinary excretion of the mercapturic acid of acrolein/crotonaldehyde between post intervention and baseline.
Time frame: Baseline up to 14 days post intervention
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avmacol | Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde | Urindary excretion of mercapturic acid of acrolein | 1.11 data presented as ratio; no unit |
| Avmacol | Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde | Urinary excretion of mercapturic acid of crotonaldehyde | 1.05 data presented as ratio; no unit |
| Avmacol 8 Tablets | Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde | Urindary excretion of mercapturic acid of acrolein | 1.28 data presented as ratio; no unit |
| Avmacol 8 Tablets | Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde | Urinary excretion of mercapturic acid of crotonaldehyde | 1.18 data presented as ratio; no unit |
Secondary
Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens
Dose-response relationship between the Avmacol dose and the detoxification of tobacco carcinogens. Data presented as ratio of percent change of the overnight urinary excretion of mercapturic acid of benzene/acrolein/crotonaldehyde between the 8 tables and 4 tables dose.
Time frame: Up to 14 days post intervention
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avmacol | Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens | Mercapturic acid of benzene | 1.01 data presented as ratio; no unit |
| Avmacol | Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens | Mercapturic acid of acrolein | 1.14 data presented as ratio; no unit |
| Avmacol | Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens | Mercapturic acid of crotonaldehyde | 1.12 data presented as ratio; no unit |
Secondary
Systemic Study Agent Exposure
Change in the total urinary levels of sulforaphane and its glutathione-derived metabolites (i.e., the sum of the molar concentrations of sulforaphane and its glutathione-derived metabolites in urine). Data presented as ratio of the geometric mean of the total urinary levels of sulforaphane and its metabolites between post intervention and baseline.
Time frame: Up to 14 days post intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avmacol | Systemic Study Agent Exposure | 467.9 data presented as ratio; no unit |
| Avmacol 8 Tablets | Systemic Study Agent Exposure | 990.0 data presented as ratio; no unit |
Other Pre-specified
GSTM1 and GSTT1 Genotypes
Change in the urinary excretion of the mercapturic acids of tobacco carcinogens by GSTM1 and GSTT1 genotype. Data presented as ratio of the geometric mean of urinary excretion of mercapturic acid of benzene between post intervention and baseline for each genotype.
Time frame: Up to 14 days post intervention
Population: The data were presented by genotype. Therefore, the number of participants with a particular genotype is a subset of the overall number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avmacol | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTM1-null participants | 1.23 data presented as ratio; no unit |
| Avmacol | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTM1-positive participants | 1.10 data presented as ratio; no unit |
| Avmacol | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTT1-null participants | 0.75 data presented as ratio; no unit |
| Avmacol | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTT1-positive participants | 1.26 data presented as ratio; no unit |
| Avmacol 8 Tablets | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTT1-positive participants | 1.20 data presented as ratio; no unit |
| Avmacol 8 Tablets | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTM1-null participants | 1.34 data presented as ratio; no unit |
| Avmacol 8 Tablets | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTT1-null participants | 1.16 data presented as ratio; no unit |
| Avmacol 8 Tablets | GSTM1 and GSTT1 Genotypes | Mercapturic acid of benzene in GSTM1-positive participants | 1.06 data presented as ratio; no unit |