Effects of Avmacol® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03268993|
Recruitment Status : Completed
First Posted : August 31, 2017
Last Update Posted : April 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer Head and Neck Squamous Cell Carcinoma (HNSCC) Head and Neck Carcinoma Head and Neck Tobacco-Related Carcinoma Carcinoma in Situ Dysplasia Hyperplasia Premalignant Lesion||Dietary Supplement: Avmacol||Not Applicable|
The broccoli seed preparation, 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. This study is not designed to examine the therapeutic or reparative effects of Avmacol® on premalignant lesions of the oral cavity.
We will systematically assess the clinical chemopreventive potential of Avmacol® administration to patients with tobacco-related HNSCC at high risk for second primary tumor by:
- Conducting this phase 0 clinical study to evaluate the pharmacodynamic range of NRF2 pathway activation in the oral mucosa of HNSCC patients, in response to two tolerable and bioactive doses of Avmacol®;
- Determining whether the level of NRF2 pathway activation achieved in human oral epithelium is chemopreventive in the NQO1 murine model of environmental carcinogenesis; and
- Analyzing specimens from the Phase 0 trial to determine whether Avmacol® induces changes in alternative biomarkers of SF chemopreventive efficacy identified in the laboratory.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
Thirty-six individuals who have previously been treated for tobacco-related, HPV-negative HNSCC will be recruited for this study.
After being deemed eligible, subjects will be assigned a patient number and be registered into the CTMA database.
At registration, they will be randomized to receive either 4 tablets/day in Cycle 1 or 8 tablets/day in Cycle 1 (and the other dose in Cycle 2). This randomization is not blinded. Randomization will be stratified by history of head and neck radiation therapy (yes or no).
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|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|
|Actual Study Start Date :||July 27, 2018|
|Actual Primary Completion Date :||July 22, 2019|
|Actual Study Completion Date :||July 22, 2019|
You will be given a higher dose of Avmacol® each month, taking 2 Avmacol® tablets per day the first month (Cycle 1), 4 Avmacol® tablets per day the second month (Cycle 2), and 8 Avmacol® tablets per day the third month (Cycle 3). Investigators will study how Avmacol® affects your body by collecting three different tissues: 1) your cheek cells (buccal cells); 2) your urine; and 3) your blood. After you have finished three months of Avmacol®, you will return one month later for an end-of-study visit.
Dietary Supplement: Avmacol
Avmacol is a dietary supplement available over the counter
Other Name: broccoli see extract
- Change in NRF2 target gene expression [ Time Frame: From baseline throughout treatment period, up to 4 months ]Quantitative changes in NRF2 target gene transcripts expression (i.e. NQO1 and GCLC) in oral mucosa (buccal cytobrush) by quantitative polymerase chain reaction (qPCR) according to a linear mixed model framework.
- Change in NRF2 target proteins [ Time Frame: From baseline throughout treatment period, up to 4 months ]Changes in NRF2 target proteins in buccal punch biopsies by immunoblotting.
- Change in NRF2 target gene transcripts [ Time Frame: From baseline throughout treatment period, up to 4 months ]Change in NRF2 target gene transcripts, between the two doses of Avmacol® by immunoblotting.
- Change in NRF2-independent proteins [ Time Frame: From baseline throughout treatment period, up to 4 months ]Change in NRF2 target gene transcripts, between the two doses of Avmacol® by immunoblotting.
- Alterations of Avmacol® activity in PBMCs - NK cells [ Time Frame: From baseline throughout treatment period, up to 4 months ]Changes in Peripheral Blood Mononuclear Cells (PBMC) gene expression and flow cytometry patterns in NK cells.
- Alterations of Avmacol® activity in PBMCs - T cells [ Time Frame: From baseline throughout treatment period, up to 4 months ]Changes in Peripheral Blood Mononuclear Cells (PBMC) gene expression and flow cytometry patterns in T cells.
- Change in serum cytokine levels [ Time Frame: From baseline throughout treatment period, up to 4 months ]Change in serum cytokine levels, as determined by multiplexed bead-based cytokine assays.
- Measurement of serum albumin-bound SF [ Time Frame: From baseline throughout treatment period, up to 4 months ]Measurement of urinary metabolites of SF using isotope dilution mass spectrometry.
- Safety profile in accordance with NCI CTCAE v.4 [ Time Frame: Throughout treatment period, up to 4 months ]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
- Proportion of patients primary tumors harboring genomic alteration of NRF2 related genes [ Time Frame: At baseline ]Genomic alterations in primary tumors will be characterized and the proportion determined by number of patients with NRF2 related genes per the total number of patients studied.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03268993
|United States, Pennsylvania|
|UPMC Eye Center - Eye and Ear Institute|
|Pittsburgh, Pennsylvania, United States, 15213|
|UPMC Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Dan P Zandberg, MD||University of Pittsburgh|