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

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.

Inclusion Criteria:

- Patients 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
human papillomavirus (HPV) negative as defined by routine p16 IHC at the local site.

- Patients may be enrolled between 3 months and 5 years AFTER completion of
curative-intent therapy (including surgery, radiotherapy, and/or chemotherapy).

- Patients 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.

- Patients must have a Karnofsky Performance Status of 80% or higher or an Eastern
Cooperative Oncology Group (ECOG) of 0-1

- Current and former tobacco users are eligible.

- 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.

Exclusion Criteria:

- Patient has 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 immunohistochemistry.

- 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

- Chronic use of steroids at immunosuppressive doses.

- History of severe food intolerance to broccoli.