Head and Neck CancerNCT03268993
Effects of Avmacol® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer
A study testing Avmacol in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma (HNSCC), run by University of Pittsburgh at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), Head and Neck Carcinoma
- What is being tested?
- Avmacol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Jul 2018to 22 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have completed curative-intent therapy (including surgery, radiation, and/or chemotherapy) for a first tobacco-related oral premalignant lesion (OPL) or HNSCC of any stage (eligible lesions include high grade dysplasia; carcinoma in situ; or stage I-IVa HNSCC).
- Primary site may include oral cavity, pharynx, or larynx. Oropharynx primaries must be HPV (-) as defined by routine p16 IHC at the local site.
- Participants may be enrolled between 3 months and 5 years AFTER completion of curative-intent therapy (including surgery, radiotherapy, and/or chemotherapy).
- Participants may have untreated OPLs (i.e., hyperplasia, dysplasia, carcinoma in situ) at the time of study entry, provided the index OPL or HNSCC was definitively treated.
- Participants must be at least 18 years old.
- Participants must have a Karnofsky Performance Status of 80% or higher or an ECOG of 0-1 (Appendix A).
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- Current and former tobacco users are eligible. The tobacco use assessment form must be completed following consent, to assure eligibility (Appendix B). Patients must have ≥10 pack-year cumulative tobacco exposure or its equivalent to be eligible. This is defined as follows:
- Cigarette exposure: ≥10 pack-years OR
- Cigar exposure: ≥ 10 cigar-years, where 1 cigar year is defined as having smoked on average ≥ 1 cigar/day for a year OR
- Chewing tobacco: ≥10 snuff-years, where 1 snuff year is defined as using on average ≥ 1 pinch (dip) of chewing tobacco/day for a year.
- Able to perform written, informed consent.
- Women of childbearing potential (WCBP) must have a negative urine pregnancy test within 7 Days prior to the first study intervention.
- WCBP 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 she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation.
Who cannot join
- Participants have a history of another malignancy within 2 years prior to starting study treatment, except for excised and cured carcinoma-in-situ of breast or cervix; non-melanomatous skin cancer; T1-2, N0, M0 differentiated thyroid carcinoma either resected or under active surveillance; superficial bladder cancer; T1a or T1b prostate cancer comprising < 5% of resected tissue with normal prostate specific antigen (PSA) since resection, or status post external beam radiation or brachytherapy with normal PSA since radiation.
- Primary oropharyngeal HNSCC which is HPV (+) as defined by p16 IHC.
- Participants with acute intercurrent illness or those who had major surgery within the preceding 4 weeks unless they have fully recovered.
- Participants who have a positive pregnancy test, are pregnant, or breast feeding.
- Patients who are not practicing adequate contraception are ineligible if they are of child bearing potential.
- Patients currently using anti-neoplastic or anti-tumor agents, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy.
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- Chronic anticoagulation with warfarin. Patients on low molecular weight heparin or fondaparinux may be enrolled.
- Use of chronic prescribed medications which are potent inducers or inhibitors of CYP3A4 (Appendix C).
- Chronic use of steroids at immunosuppressive doses. (Note, physiologic replacement doses of glucocorticoid or mineralocorticoid are acceptable, eg. prednisone 5-10 mg/day; fludrocortisone 0.1-0.2 mg/day.)
- History of severe food intolerance to broccoli.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UPMC Eye Center - Eye and Ear Institute
Pittsburgh, Pennsylvania, 15213
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: 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
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.
Read the detailed description
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:
- 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®;
- Determining whether the level of NRF2 pathway activation achieved in human oral epithelium is chemopreventive in the NQO1 murine model of environmental carcinogenesis; and
- Analyzing specimens from the Phase 0 trial to determine whether Avmacol® induces changes in alternative biomarkers of SF chemopreventive efficacy identified in the laboratory.
- Conditions
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), Head and Neck Carcinoma, Head and Neck, Tobacco-Related Carcinoma, Carcinoma in Situ
- Being tested
- Avmacol
- Keywords
- prevention, dietary supplement, broccoli, avmacol
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma in Situ, Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvmacolDietary supplement
Also called broccoli see extract
Avmacol is a dietary supplement available over the counter
| Study group | Role | What they receive |
|---|---|---|
| Avmacol | Other | 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. Receives: Dietary Supplement: Avmacol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in NRF2 target gene expression
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.
Measured: From baseline throughout treatment period, up to 4 months
Secondary outcomes (9)
Change in NRF2 target proteins
Changes in NRF2 target proteins in buccal punch biopsies by immunoblotting.
Measured: From baseline throughout treatment period, up to 4 months
Change in NRF2 target gene transcripts
Change in NRF2 target gene transcripts, between the two doses of Avmacol® by immunoblotting.
Measured: From baseline throughout treatment period, up to 4 months
Change in NRF2-independent proteins
Change in NRF2 target gene transcripts, between the two doses of Avmacol® by immunoblotting.
Measured: From baseline throughout treatment period, up to 4 months
Alterations of Avmacol® activity in PBMCs - NK cells
Changes in Peripheral Blood Mononuclear Cells (PBMC) gene expression and flow cytometry patterns in NK cells.
Measured: From baseline throughout treatment period, up to 4 months
Alterations of Avmacol® activity in PBMCs - T cells
Changes in Peripheral Blood Mononuclear Cells (PBMC) gene expression and flow cytometry patterns in T cells.
Measured: From baseline throughout treatment period, up to 4 months
Change in serum cytokine levels
Change in serum cytokine levels, as determined by multiplexed bead-based cytokine assays.
Measured: From baseline throughout treatment period, up to 4 months
Measurement of serum albumin-bound SF
Measurement of urinary metabolites of SF using isotope dilution mass spectrometry.
Measured: From baseline throughout treatment period, up to 4 months
Safety profile in accordance with NCI CTCAE v.4
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
Measured: Throughout treatment period, up to 4 months
Proportion of patients primary tumors harboring genomic alteration of NRF2 related genes
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.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2017
- Study start27 Jul 2018
- Primary completion22 Jul 2019
- Study completion22 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), University of Arizona
- Responsible party
- Principal investigator, Dan Zandberg, University of Pittsburgh
- Investigators
- Dan P Zandberg, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03268993
- Sponsor's protocol ID
- 18-028
- Status last verified
- Apr 2023
- First submitted
- 10 Jul 2017
- Last updated
- 7 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03268993
- Acronym / sponsor ID
- 18-028
- Conditions
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), Head and Neck Carcinoma, Head and Neck, Tobacco-Related Carcinoma, Carcinoma in Situ
- Keywords
- prevention, dietary supplement, broccoli, avmacol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), University of Arizona
- Study start
- 27 Jul 2018 (actual)
- Primary completion
- 22 Jul 2019 (actual)
- Study completion
- 22 Jul 2019 (actual)
- First posted
- 31 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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®;
- Determining whether the level of NRF2 pathway activation achieved in human oral epithelium is chemopreventive in the NQO1 murine model of environmental carcinogenesis; and
- Analyzing specimens from the Phase 0 trial to determine whether Avmacol® induces changes in alternative biomarkers of SF chemopreventive efficacy identified in the laboratory.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Avmacol | Other | Dietary Supplement: AvmacolYou 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants must have completed curative-intent therapy (including surgery, radiation, and/or chemotherapy) for a first tobacco-related oral premalignant lesion (OPL) or HNSCC of any stage (eligible lesions include high grade dysplasia; carcinoma in situ; or stage I-IVa HNSCC).
- Primary site may include oral cavity, pharynx, or larynx. Oropharynx primaries must be HPV (-) as defined by routine p16 IHC at the local site.
- Participants may be enrolled between 3 months and 5 years AFTER completion of curative-intent therapy (including surgery, radiotherapy, and/or chemotherapy).
- Participants may have untreated OPLs (i.e., hyperplasia, dysplasia, carcinoma in situ) at the time of study entry, provided the index OPL or HNSCC was definitively treated.
- Participants must be at least 18 years old.
Key exclusion criteria (10 listed)
- Participants have a history of another malignancy within 2 years prior to starting study treatment, except for excised and cured carcinoma-in-situ of breast or cervix; non-melanomatous skin cancer; T1-2, N0, M0 differentiated thyroid carcinoma either resected or under active surveillance; superficial bladder cancer; T1a or T1b prostate cancer comprising < 5% of resected tissue with normal prostate specific antigen (PSA) since resection, or status post external beam radiation or brachytherapy with normal PSA since radiation.
- Primary oropharyngeal HNSCC which is HPV (+) as defined by p16 IHC.
- Participants with acute intercurrent illness or those who had major surgery within the preceding 4 weeks unless they have fully recovered.
- Participants who have a positive pregnancy test, are pregnant, or breast feeding.
- Patients who are not practicing adequate contraception are ineligible if they are of child bearing potential.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvmacolAlso: broccoli see extractAvmacol is a dietary supplement available over the counter | Dietary supplement | Avmacol |
Primary outcome
Change in NRF2 target gene expression
Time frame: From baseline throughout treatment period, up to 4 months
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.
9 secondary outcomes
Change in NRF2 target proteins
Time frame: From baseline throughout treatment period, up to 4 months
Change in NRF2 target gene transcripts
Time frame: From baseline throughout treatment period, up to 4 months
Change in NRF2-independent proteins
Time frame: From baseline throughout treatment period, up to 4 months
Alterations of Avmacol® activity in PBMCs - NK cells
Time frame: From baseline throughout treatment period, up to 4 months
Alterations of Avmacol® activity in PBMCs - T cells
Time frame: From baseline throughout treatment period, up to 4 months
Change in serum cytokine levels
Time frame: From baseline throughout treatment period, up to 4 months
Measurement of serum albumin-bound SF
Time frame: From baseline throughout treatment period, up to 4 months
Safety profile in accordance with NCI CTCAE v.4
Time frame: Throughout treatment period, up to 4 months
Proportion of patients primary tumors harboring genomic alteration of NRF2 related genes
Time frame: At baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan P Zandberg, MD principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Avmacol in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma (HNSCC), run by University of Pittsburgh at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in NRF2 target gene expression (time frame: From baseline throughout treatment period, up to 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2023.