Clinical trial NCT03182959: Broccoli Sprout Extract in Preventing Recurrence in Patients With Tobacco-Related Head and Neck Squamous Cell Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: HNSCC
Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Tobacco-Related Carcinoma
Carcinoma in Situ
Dysplasia
Hyperplasia
Premalignant Lesion
Keywords: Nrf2 pathway
Oral mucosa
HNSCC
Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Avmacol
Tobacco-related Head and Neck Cancer
broccoli sprout powder
broccoli seed extract powder
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-06-09
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be randomized to receive either 50 mg glucoraphanin (GR) in Cycle 1 and 100 mg GR in cycle 2, or 100 mg GR in Cycle 1 and 50 mg GR in Cycle 2, but all participants will receive both doses.
Primary purpose: PREVENTION

Brief summary: This 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine whether 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 HNSCC.
timeFrame: 4 months
Secondary outcomes:
measure: Determine whether NRF2 target protein expression is upregulated by Avmacol® in the oral mucosa.
timeFrame: 4 months
measure: Evaluate for a dose-response relationship between Avmacol® dose and quantitative change in candidate NRF2 pathway biomarkers in oral mucosa.
timeFrame: 4 months
measure: Evaluate oral mucosa for quantitative modulation of NRF2-independent biomarkers of sulforaphane (SF) chemopreventive efficacy, as defined in parallel preclinical models.
timeFrame: 4 months
measure: Evaluate biomarkers of Avmacol® activity in PBMCs gene expression
timeFrame: 4 months
measure: Evaluate biomarkers of Avmacol® activity in PBMCs flow cytometry
timeFrame: 4 months
measure: Evaluate biomarkers of Avmacol® activity in PBMCs functional assays of T cells and NK cells
timeFrame: 4 months
measure: Evaluate cytokine biomarkers of Avmacol® activity in serum, including CXCL8, Interleukin 8 (IL8).
timeFrame: 4 months
measure: Measurement of serum albumin-bound SF using isotope dilution mass spectrometry.
timeFrame: 4 months
measure: Measure urinary metabolites of SF during administration of two doses of Avmacol®.
timeFrame: 4 months
measure: Description of safety profile in accordance with NCI CTCAE v.4.
timeFrame: 4 months
measure: Description of the proportion of patients with HNSCC primary tumors harboring genomic alteration of NRF2.
timeFrame: 4 months
measure: Description of the proportion of patients with HNSCC primary tumors harboring genomic alteration of NRF2 related genes.
timeFrame: 4 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
Study officials:
affiliation: The University of Arizona
name: Julie E. Bauman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: