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

NCT03268993 | Completed DMC

• 1 other identifier: 18-028
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief 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. In this study, participants who have been curatively treatment for head and neck cancer, will take Avmacol twice a day for 3 months.

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; Dysplasia; Hyperplasia; Premalignant Lesion

Keywords

prevention; dietary supplement; broccoli; avmacol

Outcome Measures

Primary Outcomes (1)

• 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.

  From baseline throughout treatment period, up to 4 months

Secondary Outcomes (9)

• Change in NRF2 target proteins

  From baseline throughout treatment period, up to 4 months

• Change in NRF2 target gene transcripts

  From baseline throughout treatment period, up to 4 months

• Change in NRF2-independent proteins

  From baseline throughout treatment period, up to 4 months

• Alterations of Avmacol® activity in PBMCs - NK cells

  From baseline throughout treatment period, up to 4 months

• Alterations of Avmacol® activity in PBMCs - T cells

  From baseline throughout treatment period, up to 4 months

Study Arms (1)

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.

Dietary Supplement: Avmacol

Interventions

Avmacol DIETARY_SUPPLEMENT

Avmacol is a dietary supplement available over the counter

Also known as: broccoli see extract

Avmacol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Cancer Institute (NCI): collaborator
• University of Arizona: collaborator

Study Sites (2)

UPMC Eye Center - Eye and Ear Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma in Situ; Hyperplasia

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dan P Zandberg, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: August 31, 2017
• Study Start: July 27, 2018
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: April 7, 2023

Record last verified: 2023-04

Locations

US (2)