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

Inclusion Criteria:

1. 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; carcinomain situ; or stage I-IVa HNSCC).
2. Primary site may include oral cavity, pharynx, or larynx. Oropharynx primaries must beHPV (-) as defined by routine p16 IHC at the local site.
3. Participants may be enrolled between 3 months and 5 years AFTER completion ofcurative-intent therapy (including surgery, radiotherapy, and/or chemotherapy).
4. 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.
5. Participants must be at least 18 years old.
6. Participants must have a Karnofsky Performance Status of 80% or higher or an ECOG of 0-1 (Appendix A).
7. Current and former tobacco users are eligible. The tobacco use assessment form must becompleted following consent, to assure eligibility (Appendix B). Patients must have ≥10 pack-year cumulative tobacco exposure or its equivalent to be eligible. This isdefined as follows:
8. Cigarette exposure: ≥10 pack-years OR
9. Cigar exposure: ≥ 10 cigar-years, where 1 cigar year is defined as having smokedon average ≥ 1 cigar/day for a year OR
10. Chewing tobacco: ≥10 snuff-years, where 1 snuff year is defined as using onaverage ≥ 1 pinch (dip) of chewing tobacco/day for a year.
11. Able to perform written, informed consent.
12. Women of childbearing potential (WCBP) must have a negative urine pregnancy testwithin 7 Days prior to the first study intervention.
13. WCBP and men must agree to use adequate contraception (hormonal or barrier method ofbirth control; abstinence) prior to study entry and for the duration of studyparticipation. Should a woman become pregnant or suspect she is pregnant while she orher partner is participating in this study, she should inform her treating physicianimmediately. Men treated or enrolled on this protocol must also agree to use adequatecontraception prior to the study and for the duration of study participation.

Exclusion Criteria:

1. Participants have a history of another malignancy within 2 years prior to startingstudy treatment, except for excised and cured carcinoma-in-situ of breast or cervix;non-melanomatous skin cancer; T1-2, N0, M0 differentiated thyroid carcinoma eitherresected or under active surveillance; superficial bladder cancer; T1a or T1b prostatecancer comprising < 5% of resected tissue with normal prostate specific antigen (PSA)since resection, or status post external beam radiation or brachytherapy with normalPSA since radiation.
2. Primary oropharyngeal HNSCC which is HPV (+) as defined by p16 IHC.
3. Participants with acute intercurrent illness or those who had major surgery within thepreceding 4 weeks unless they have fully recovered.
4. Participants who have a positive pregnancy test, are pregnant, or breast feeding.
5. Patients who are not practicing adequate contraception are ineligible if they are ofchild bearing potential.
6. Patients currently using anti-neoplastic or anti-tumor agents, including chemotherapy,radiation therapy, immunotherapy, and hormonal anticancer therapy.
7. Chronic anticoagulation with warfarin. Patients on low molecular weight heparin orfondaparinux may be enrolled.
8. Use of chronic prescribed medications which are potent inducers or inhibitors ofCYP3A4 (Appendix C).
9. Chronic use of steroids at immunosuppressive doses. (Note, physiologic replacementdoses of glucocorticoid or mineralocorticoid are acceptable, eg. prednisone 5-10mg/day; fludrocortisone 0.1-0.2 mg/day.)
10. History of severe food intolerance to broccoli.