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

NCT03182959 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 16120327625P50CA097190
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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. 1.To learn whether the dietary supplement, Avmacol®, can stimulate cheek cells to repair damage from environmental toxins;
2. 2.to learn how the body metabolizes Avmacol®, by measuring its byproducts in the participant's urine and blood;
3. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Quantitative changes in NRF2 target gene transcripts (i.e. NAD(P)H Quinone Dehydrogenase 1 \[NQO1\] and GCLC) in buccal cytobrush by quantitative polymerase chain reaction (qPCR) according to a linear mixed model framework.

  4 months

Secondary Outcomes (12)

• Determine whether NRF2 target protein expression is upregulated by Avmacol® in the oral mucosa.

  4 months

• Evaluate for a dose-response relationship between Avmacol® dose and quantitative change in candidate NRF2 pathway biomarkers in oral mucosa.

  4 months

• Evaluate oral mucosa for quantitative modulation of NRF2-independent biomarkers of sulforaphane (SF) chemopreventive efficacy, as defined in parallel preclinical models.

  4 months

• Evaluate biomarkers of Avmacol® activity in PBMCs gene expression

  4 months

• Evaluate biomarkers of Avmacol® activity in PBMCs flow cytometry

  4 months

Study Arms (2)

Lower dose, higher dose

EXPERIMENTAL

During the first cycle, the patient will self-administer Avmacol® (70 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer four tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary. During the second cycle, the patient will self-administer Avmacol® (140 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer eight tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary.

Drug: Avmacol®

Higher dose, lower dose

EXPERIMENTAL

During the first cycle, the patient will self-administer Avmacol® (140 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer eight tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary. During the second cycle, the patient will self-administer Avmacol® (70 μmol/day SF equivalent) starting on the evening of Day 1 of the cycle. Participants will self-administer four tablets of Avmacol® every evening, ideally between 4 pm and 8 pm, through the evening of Day 28. Participants will record the date and time of each Avmacol® administration on the provided diary.

Drug: Avmacol®

Interventions

Avmacol® DRUG

Avmacol® tablets

Also known as: Broccoli Sprout Extract

Higher dose, lower dose; Lower dose, higher dose

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

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

Study Officials

• Julie E. Bauman, MD, MPH

  The University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 18, 2017
• First Posted: June 9, 2017
• Study Start: April 24, 2017
• Primary Completion: January 1, 2020
• Study Completion: January 19, 2021
• Last Updated: June 21, 2021

Record last verified: 2021-06

Locations

US (1)