Antineoplastic Agents

All Drugs and Chemicals

Other Dietary Supplements

Sulforaphane

Protective Agents

Buccal cells line the inner cheek, and will be collected from the inner right cheek with a cytobrush (a q-tip like swab) by a trained investigator.

During the second week the participant will take 8 Avmacol tablets every evening for 3 evenings (Day 2, 3, 4), and record the time of each dose in the provided diary. Research blood collection: on days 1 and 5. Overnight urine collection.

Avmacol is an over-the-counter mixture of broccoli seed and sprout extracts in tablet form to promote detoxification. These tablets contain natural substances that stimulate the body's own defense mechanisms against toxic substances commonly encountered in the environment, such as air pollution and tobacco smoke.

Avmacol

Julie Bauman, MD

Avmacol is an over-the-counter dietary supplement containing broccoli seed and sprout extracts in tablet form, hypothesized to activate protective cellular pathways including detoxication. In this study, healthy volunteers will take 3 days of Avmacol in order to evaluate both bioavailability and its bioactivity in cheek cells.

Avmacol is an over-the counter dietary supplement containing broccoli seed and sprout extracts in tablet form. Natural plant substances within Avmacol, called phytochemicals, are hypothesized to stimulate the body's own defense mechanisms against toxic substances commonly encountered in the environment, such as air pollution and tobacco smoke. The purpose of this study is twofold: 1) to assess the protective effects of Avmacol on the mucosa (cheek cells) of healthy volunteers, and 2) to assess the collection of cheek cells by scraping, as a less invasive method of studying drug effects in the body compared to drawing blood or a tissue biopsy. Ultimately, these results will be used to design a larger study of Avmacol in patients with tobacco-related head and neck cancer. Avmacol will be studied as a way to possibly prevent a second cancer from developing in these patients.

Bioavailability and Mucosal Bioactivity of Avmacol® in Healthy Volunteers

A Pilot Study Evaluating the Bioavailability and Mucosal Bioactivity of the Dietary Supplement, Avmacol®, in Healthy Volunteers With Optimization of Buccal Cell Biomarkers

Number of buccal cells collected by cytobrush during week 1 (days 1-5) of the study

Quantitative mRNA for NQO1 in buccal cells at baseline (day 1) vs. buccal cells taken during the 3 days of Avmacol (days 2-4), and the day after Avmacol (day 5)

University of Pittsburgh

MD, MPH

Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma in Situ

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Hyperplasia

Precancerous Conditions

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

You will be given a higher dose of Avmacol® each month, taking 2 Avmacol® tablets per day the first month (Cycle 1), 4 Avmacol® tablets per day the second month (Cycle 2), and 8 Avmacol® tablets per day the third month (Cycle 3). Investigators will study how Avmacol® affects your body by collecting three different tissues: 1) your cheek cells (buccal cells); 2) your urine; and 3) your blood. After you have finished three months of Avmacol®, you will return one month later for an end-of-study visit.

Avmacol is a dietary supplement available over the counter

Dan P Zandberg, MD

Avmacol is an over-the-counter dietary supplement containing broccoli seed and sprout extracts in tablet form, hypothesized to activate protective cellular pathways including detoxication. In this study, participants who have been curatively treatment for head and neck cancer, will take Avmacol twice a day for 3 months.

The broccoli seed preparation, Avmacol®, results in acute and/or sustained induction of NRF2 target gene transcripts in the oral mucosa of patients who have been curatively treated for a tobacco-related head and neck squamous cell carcinoma (HNSCC), including high grade dysplasia, carcinoma in situ, or invasive carcinoma. This study is not designed to examine the therapeutic or reparative effects of Avmacol® on premalignant lesions of the oral cavity.

We will systematically assess the clinical chemopreventive potential of Avmacol® administration to patients with tobacco-related HNSCC at high risk for second primary tumor by:

1. Conducting this phase 0 clinical study to evaluate the pharmacodynamic range of NRF2 pathway activation in the oral mucosa of HNSCC patients, in response to two tolerable and bioactive doses of Avmacol®;
2. Determining whether the level of NRF2 pathway activation achieved in human oral epithelium is chemopreventive in the NQO1 murine model of environmental carcinogenesis; and
3. Analyzing specimens from the Phase 0 trial to determine whether Avmacol® induces changes in alternative biomarkers of SF chemopreventive efficacy identified in the laboratory.

Thirty-six individuals who have previously been treated for tobacco-related, HPV-negative HNSCC will be recruited for this study.

After being deemed eligible, subjects will be assigned a patient number and be registered into the CTMA database.

At registration, they will be randomized to receive either 4 tablets/day in Cycle 1 or 8 tablets/day in Cycle 1 (and the other dose in Cycle 2). This randomization is not blinded. Randomization will be stratified by history of head and neck radiation therapy (yes or no).

Effects of Avmacol® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer

A Phase 0 Study Evaluating the Systemic Bioavailability and Pharmacodynamic Effects of Avmacol® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer

Quantitative changes in NRF2 target gene transcripts expression (i.e. NQO1 and GCLC) in oral mucosa (buccal cytobrush) by quantitative polymerase chain reaction (qPCR) according to a linear mixed model framework.

Changes in NRF2 target proteins in buccal punch biopsies by immunoblotting.

Change in NRF2 target gene transcripts, between the two doses of Avmacol® by immunoblotting.

Changes in Peripheral Blood Mononuclear Cells (PBMC) gene expression and flow cytometry patterns in NK cells.

Changes in Peripheral Blood Mononuclear Cells (PBMC) gene expression and flow cytometry patterns in T cells.

Change in serum cytokine levels, as determined by multiplexed bead-based cytokine assays.

Measurement of urinary metabolites of SF using isotope dilution mass spectrometry.

Patients will receive a diary for daily logging of adverse events. This will tabulated by Avmacol dose and type and grade of adverse events. The mean frequency and grade of events will be calculated by dose, and between-dose differences compared by means

Genomic alterations in primary tumors will be characterized and the proportion determined by number of patients with NRF2 related genes per the total number of patients studied.

National Cancer Institute (NCI)

University of Arizona

Principal Investigator

Recurrence

Neoplasms, Squamous Cell

During the first cycle, the patient will self-administer Avmacol® (70 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer four tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary.

During the second cycle, the patient will self-administer Avmacol® (140 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer eight tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary.

During the first cycle, the patient will self-administer Avmacol® (140 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer eight tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary.

During the second cycle, the patient will self-administer Avmacol® (70 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer four tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary.

Avmacol®

Julie E. Bauman, MD, MPH

This study is being done to see whether Avmacol®, a dietary supplement made from broccoli sprout and seed extract powder, induces changes in inner cheek cells that may be protective against environmental toxins such as tobacco.

There are three main goals of the study:

1. To learn whether the dietary supplement, Avmacol®, can stimulate cheek cells to repair damage from environmental toxins;
2. to learn how the body metabolizes Avmacol®, by measuring its byproducts in the participant's urine and blood;
3. to learn whether the immune system can be stimulated by Avmacol®, by studying the natural killer cells and T cells in the participant's blood.

This study hypothesizes that nuclear factor erythroid 2-related factor 2 (NRF2) pathway activation in oral epithelium can be induced by administering Avmacol® to patients curatively treated for a first tobacco-related HNSCC.

The aim of this Phase 0 clinical study is to determine the oral bioavailability of sulforaphane in the commercially available dietary supplement, Avmacol®, and to determine the level of pharmacodynamic upregulation of NRF2 target gene transcripts that occurs in the oral epithelium of patients who have completed curative treatment for tobacco-related HNSCC, including high grade dysplasia, carcinoma in situ, or invasive carcinoma.

Participants will be randomized to receive either 50 mg glucoraphanin (GR) in Cycle 1 and 100 mg GR in cycle 2, or 100 mg GR in Cycle 1 and 50 mg GR in Cycle 2, but all participants will receive both doses.

Broccoli Sprout Extract in Preventing Recurrence in Patients With Tobacco-Related Head and Neck Squamous Cell Cancer

Quantitative changes in NRF2 target gene transcripts (i.e. NAD(P)H Quinone Dehydrogenase 1 \[NQO1\] and GCLC) in buccal cytobrush by quantitative polymerase chain reaction (qPCR) according to a linear mixed model framework.

Change in NRF2 target proteins in buccal punch biopsies by immunoblotting.

Acute change in NRF2 target gene transcripts, as compared to baseline, between the two doses of Avmacol®.

Change in NRF2-independent proteins by immunoblotting, eg. STAT3, phospho-STAT3 (pSTAT3).

Alterations in Peripheral Blood Mononuclear Cells (PBMC) gene expression patterns

Alterations in Peripheral Blood Mononuclear Cells (PBMC) immune cell sub-populations

Alterations in Peripheral Blood Mononuclear Cells (PBMC) Tcell/ Natural Killer (NK) cell function

Sulforaphane metabolites will be assessed in overnight urine collected following the first dose of each cycle. The steady state concentration of broccoli seed preparations will be characterized by measuring albumin-bound sulforaphane in serum collected on the last day of each cycle. This assay represents an integrated measure of sulforaphane exposure, which will be correlated with biomarker modulation by means of repeated measures analysis of covariance.

Patients will receive a diary for daily logging of adverse events. This will tabulated by Avmacol dose and type and grade of adverse events. The mean frequency and grade of events will be calculated by dose, and between-dose differences compared by means of mixed effects analysis of covariance.

Describe the genetic profile of NRF2 within the index HNSCC primary tumor in the target population.

Archived tumor specimens from the index tobacco-related head and neck squamous cell carcinoma will be collected. Tumor specimens analyzed for genomic alterations in NRF2 and related genes. The frequency of genomic alterations will be characterized.

Describe the genetic profile of other related genes within the index HNSCC primary tumor in the target population.

Archived tumor specimens from the index tobacco-related head and neck squamous cell carcinoma will be collected. Tumor specimens analyzed for genomic alterations in NRF2 and related genes. The frequency of genomic alterations will be characterized.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bioavailability and Mucosal Bioactivity of Avmacol® in Healthy Volunteers	NCT02800265	Healthy	Avmacol	18 Years -	University of Pittsburgh
Effects of Avmacol® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer	NCT03268993	Head and Neck C... Head and Neck S... Head and Neck C... Head and Neck Tobacco-Related... Carcinoma in Si... Dysplasia Hyperplasia Premalignant Le...	Avmacol	18 Years -	University of Pittsburgh
Effects of Avmacol® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer	NCT03268993	Head and Neck C... Head and Neck S... Head and Neck C... Head and Neck Tobacco-Related... Carcinoma in Si... Dysplasia Hyperplasia Premalignant Le...	Avmacol	18 Years -	University of Pittsburgh
Broccoli Sprout Extract in Preventing Recurrence in Patients With Tobacco-Related Head and Neck Squamous Cell Cancer	NCT03182959	HNSCC Head and Neck C... Head and Neck S... Tobacco-Related... Carcinoma in Si... Dysplasia Hyperplasia Premalignant Le...	Avmacol®	18 Years -	University of Arizona

Spots Global Cancer Trial Database for avmacol

Every month we try and update this database with for avmacol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for avmacol

Every month we try and update this database with for avmacol cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for avmacol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.