Testing the Effect of the Broccoli Seed and Sprout Extract, Avmacol ES, on the Cancer Causing Substances of Tobacco in Heavy Smokers

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cigarette Smoking-Related Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Drug: Placebo Administration; Procedure: Biospecimen Collection; Dietary supplement: Broccoli Sprout/Broccoli Seed Extract Supplement

Detailed Description

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 and nasal epithelial cell samples at visits 2 and 6 and the collection of buccal cell samples at visits 2, 3, and 6.

GROUP II: Patients receive placebo PO QD for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood and nasal epithelial cell samples at visits 2 and 6 and the collection of buccal cell samples at visits 2, 3, and 6.

After completion of study, patients are followed up at 2-4 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Recruiting
      • University of Arizona Cancer Center - Prevention Research Clinic
      • Principal Investigator: Linda L. Garland
      • Contact: Linda L. Garland; Phone Number: 202-994-0329
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Recruiting
      • George Washington University Medical Center
      • Principal Investigator: Julie E. Bauman
      • Contact: Julie E. Bauman; Phone Number: 202-994-0329; Email: jebauman@gwu.edu
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Contact: Martin C. Mahoney; Phone Number: 716-845-2300; Email: Martin.Mahoney@RoswellPark.org
      • Principal Investigator: Martin C. Mahoney

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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. No upper age limit
• 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
• Participants with known human immunodeficiency virus (HIV) infection are not eligible for this trial due to potential interaction between sulforaphane and anti-retroviral therapy
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment are not eligible due to potential interaction between sulforaphane and anti-retroviral therapy
• 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
• Participants with known chronic hepatitis B virus (HBV) infection are not eligible for this trial due to potential interaction between sulforaphane and suppressive anti-viral therapy

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

• Ongoing use of a nutraceutical or dietary supplement containing glucoraphanin or sulforaphane

  • Note, participants will be eligible if they agree to stop the glucoraphanin or sulforaphane product at least 7 days prior to the baseline visit (7-day washout)
• 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
• Any other condition or lifestyle factor, that, in the opinion of the principal investigator, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (broccoli seed and sprout extract); Patients receive broccoli seed and sprout extract PO QD for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood and nasal epithelial cell samples at visits 2 and 6 and the collection of buccal cell samples at visits 2, 3, and 6.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood, buccal cell, and nasal epithelial cell samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Dietary supplement: Broccoli Sprout/Broccoli Seed Extract Supplement; Given PO; Other Names: Avmacol
Active Comparator: Group II (placebo); Patients receive placebo PO QD for 12 weeks in the absence of unacceptable toxicity. Patients undergo the collection of blood and nasal epithelial cell samples at visits 2 and 6 and the collection of buccal cell samples at visits 2, 3, and 6.	Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given PO; Procedure: Biospecimen Collection; Undergo collection of blood, buccal cell, and nasal epithelial cell samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detoxification of benzene and acrolein	Measured by changes in the urinary levels of their respective mercapturic acids, SPMA and 3-HPMA, from baseline.	At baseline and 2, 4, 8, and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	At baseline and 2, 4, 8, and 12 weeks
Bioavailability of BSSE	Measured by urinary sulforaphane (SF) metabolites.	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).	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.	Up to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mucosal signatures of NRF2 activation, inflammation, and innate immunity	Measured by the NanoString nCounter PanCancer panel.	Baseline up to 12 weeks
Modulation of nasal epithelial gene signatures	Will assess modulation of nasal epithelial gene signatures including smoking, lung cancer, and squamous dysplasia.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Julie E Bauman, George Washington University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2022
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: November 13, 2021
• First Submitted That Met QC Criteria: November 13, 2021
• First Posted (Actual): November 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 10, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: NCI-2021-12014 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA023074 (U.S. NIH Grant/Contract); UG1CA242596 (U.S. NIH Grant/Contract); UAZ21-06-01 (Other Identifier: DCP); STUDY00000614 (Other Identifier: University of Arizona Cancer Center - Prevention Research Clinic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No