Broccoli Sprout Extract in Preventing Recurrence in Patients with Tobacco-Related Head and Neck Squamous Cell Cancer
This randomized 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.
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); NOTE: the presence of a measurable OPL at baseline is not required
- Primary site may include oral cavity, pharynx, or larynx; oropharynx primaries must be human papilloma virus (HPV) (-) as defined by routine p16 immunohistochemistry (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; the tobacco use assessment form must be completed following consent, to assure eligibility; 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
Exclusion Criteria
- Patient has a history of another malignancy within 2 years prior to starting study treatment, except for stage I-II malignancy that has been treated curatively with no clinical evidence of disease, 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 anti-coagulation 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. (Note, physiologic replacement doses of glucocorticoid or mineralocorticoid are acceptable, e.g. prednisone 5-10 mg/day; fludrocortisone 0.1-0.2 mg/day)
- History of severe food intolerance to broccoli
Additional locations may be listed on ClinicalTrials.gov for NCT03182959.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine whether the broccoli seed preparation (BSP) broccoli sprout extract (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.
SECONDARY OBJECTIVES:
I. To determine whether NRF2 target protein expression is upregulated by Avmacol in the oral mucosa.
II. To evaluate for a dose-response relationship between Avmacol dose and quantitative change in candidate NRF2 pathway biomarkers in oral mucosa.
III. To evaluate oral mucosa for quantitative modulation of NRF2-independent biomarkers of sulforaphane (SF) chemopreventive efficacy, as defined in parallel preclinical models.
IV. To evaluate biomarkers of Avmacol activity in peripheral blood mononuclear cells (PBMCs), including gene expression, flow cytometry, and functional assays of T cells and natural killer (NK) cells.
V. To evaluate cytokine biomarkers of Avmacol activity in serum, including IL-8.
VI. To describe the steady state pharmacokinetics (PK) of SF associated with two doses of Avmacol.
VII. To measure urinary metabolites of SF during administration of two doses of Avmacol.
VIII. To describe the tolerability of two chronic doses of Avmacol in our target population.
IX. To describe the genetic profile of NRF2 and related genes within the index HNSCC primary tumor in our target population.
OUTLINE: This is a dose escalation study. Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive 4 tablets of broccoli sprout extract orally (PO) daily on days 1-28 of course 1. Patients then receive 8 tablets of broccoli sprout extract PO daily on days 1-28 of course 2. Treatment repeats every 4 weeks for up to 2 courses (with a 4 week washout period between the 2 courses) in the absence of disease progression or unacceptable toxicity.
ARM 2: Patients receive 8 tablets of broccoli sprout extract PO daily on days 1-28, of course 1. Patients then receive 4 tablets of broccoli sprout extract PO daily on days 1-28 of course 2. Treatment repeats every 4 weeks for up to 2 courses (with a 4 week washout period between the 2 courses) in the absence of disease progression or unacceptable toxicity.
After completion of study, patients are followed up at 4 weeks (+/- 2 weeks).
Trial PhasePhase O
Trial Typeprevention
Lead OrganizationBanner University Medical Center - Tucson
Principal InvestigatorJulie E Bauman
- Primary ID1612032762
- Secondary IDsNCI-2017-00970, Avmacol
- ClinicalTrials.gov IDNCT03182959