Clinical Trials /

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

NCT03182959

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Nasopharyngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 1612032762
  • SECONDARY ID: 5P50CA097190
  • NCT ID: NCT03182959

Conditions

  • HNSCC
  • Head and Neck Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Tobacco-Related Carcinoma
  • Carcinoma in Situ
  • Dysplasia
  • Hyperplasia
  • Premalignant Lesion

Interventions

DrugSynonymsArms
Avmacol®Broccoli Sprout ExtractLower dose, higher dose

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Lower dose, higher doseExperimentalDuring 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.
  • Avmacol®
Higher dose, lower doseExperimentalDuring 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.
  • Avmacol®

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 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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.
Time Frame:4 months
Safety Issue:
Description:Quantitative changes in NRF2 target gene transcripts (i.e. NQO1 and GCLC) in buccal cytobrush by quantitative polymerase chain reaction (qPCR) according to a linear mixed model framework.

Secondary Outcome Measures

Measure:Determine whether NRF2 target protein expression is upregulated by Avmacol® in the oral mucosa.
Time Frame:4 months
Safety Issue:
Description:Change in NRF2 target proteins in buccal punch biopsies by immunoblotting.
Measure:Evaluate for a dose-response relationship between Avmacol® dose and quantitative change in candidate NRF2 pathway biomarkers in oral mucosa.
Time Frame:4 months
Safety Issue:
Description:Acute change in NRF2 target gene transcripts, as compared to baseline, between the two doses of Avmacol®.
Measure:Evaluate oral mucosa for quantitative modulation of NRF2-independent biomarkers of sulforaphane (SF) chemopreventive efficacy, as defined in parallel preclinical models.
Time Frame:4 months
Safety Issue:
Description:Change in NRF2-independent proteins by immunoblotting, eg. STAT3, pSTAT3.
Measure:Evaluate biomarkers of Avmacol® activity in PBMCs gene expression
Time Frame:4 months
Safety Issue:
Description:Alterations in Peripheral Blood Mononuclear Cells (PBMC) gene expression patterns
Measure:Evaluate biomarkers of Avmacol® activity in PBMCs flow cytometry
Time Frame:4 months
Safety Issue:
Description:Alterations in Peripheral Blood Mononuclear Cells (PBMC) immune cell sub-populations
Measure:Evaluate biomarkers of Avmacol® activity in PBMCs functional assays of T cells and NK cells
Time Frame:4 months
Safety Issue:
Description:Alterations in Peripheral Blood Mononuclear Cells (PBMC) Tcell/ Natural Killer (NK) cell function
Measure:Evaluate cytokine biomarkers of Avmacol® activity in serum, including IL8.
Time Frame:4 months
Safety Issue:
Description:Change in serum cytokine levels, as determined by multiplexed bead-based cytokine assays.
Measure:Measurement of serum albumin-bound SF using isotope dilution mass spectrometry.
Time Frame:4 months
Safety Issue:
Description:Sulforaphane metabolites will be assessed in overnight urine collected following the first dose of each cycle. The steady state concentration of broccoli seed preparations will be characterized by measuring albumin-bound sulforaphane in serum collected on the last day of each cycle. This assay represents an integrated measure of sulforaphane exposure, which will be correlated with biomarker modulation by means of repeated measures analysis of covariance.
Measure:Measure urinary metabolites of SF during administration of two doses of Avmacol®.
Time Frame:4 months
Safety Issue:
Description:Measurement of urinary metabolites of SF using isotope dilution mass spectrometry.
Measure:Description of safety profile in accordance with NCI CTCAE v.4.
Time Frame:4 months
Safety Issue:
Description:Patients will receive a diary for daily logging of adverse events. This will tabulated by Avmacol dose and type and grade of adverse events. The mean frequency and grade of events will be calculated by dose, and between-dose differences compared by means of mixed effects analysis of covariance.
Measure:Description of the proportion of patients with HNSCC primary tumors harboring genomic alteration of NRF2.
Time Frame:4 months
Safety Issue:
Description:Describe the genetic profile of NRF2 within the index HNSCC primary tumor in the target population. Archived tumor specimens from the index tobacco-related head and neck squamous cell carcinoma will be collected. Tumor specimens analyzed for genomic alterations in NRF2 and related genes. The frequency of genomic alterations will be characterized.
Measure:Description of the proportion of patients with HNSCC primary tumors harboring genomic alteration of NRF2 related genes.
Time Frame:4 months
Safety Issue:
Description:Describe the genetic profile of other related genes within the index HNSCC primary tumor in the target population. Archived tumor specimens from the index tobacco-related head and neck squamous cell carcinoma will be collected. Tumor specimens analyzed for genomic alterations in NRF2 and related genes. The frequency of genomic alterations will be characterized.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Arizona

Trial 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

Last Updated

June 7, 2017