This phase I clinical trial tests the immune effects of fermented wheat germ in patients with advanced solid tumor cancers who are being treated with standard of care checkpoint inhibitors. Fermented wheat germ is a nutritional supplement that some claim is a "dietary food for special medical purposes for cancer patients" to support them in treatment. There have also been claims that fermented wheat germ is "clinically proven" and "recognized by medical experts" to "enhance oncological treatment" and boost immune response to cancer; however, there are currently no documented therapeutic effects of fermented wheat germ as a nutritional supplement. Checkpoint inhibitors, given as part of standard of care for advanced solid tumors, are a type of immunotherapy that may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. The information gained from this trial may allow researchers to determine if there is any value of giving fermented wheat germ with standard of care checkpoint inhibitors for patients with advanced solid tumor malignancies.
PRIMARY OBJECTIVE: I. To assess the effect of fermented wheat germ (FWG) nutritional supplementation on natural killer (NK) cell killing activity in peripheral blood of cancer patients being treated with standard of care (SOC) immunotherapy who have voluntarily decided to take the FWG nutritional supplement. SECONDARY OBJECTIVES: I. To assess immunologic effects of FWG in subjects with cancer treated with checkpoint inhibitor (CPi)-based therapy. II. To archive stool specimens of subjects with cancer treated with CPi-based therapy for future non-interventional studies for subsequent analysis at completion of study. III. To evaluate toxicities of FWG in subjects with cancer treated with checkpoint inhibitor (CPi)-based therapy. IV. To assess immunologic effects of FWG in patients with cancer treated with CPi immune-oncology-based therapy (Immune Correlates).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Given orally (PO)
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGNatural killer (NK) cell killing activity
Proportion of patients with 20% increase of NK cell killing activity measured ex vivo on day 4 (after fermented wheat germ food supplementation only) compared to the baseline values, will be calculated, along with 95% exact confidence intervals, for each tumor type. Will also conduct a pooled analysis using data from all tumor types.
Time frame: From baseline to Day 4
NK cell activation
Production of interferon-gamma (IFNgamma), expression of activation markers (CD69) and degranulation (CD107a), a one-sided paired t-test will be used for comparison with the baseline values, and a p value of \< 0.05 will be regarded as statistically significant. Data transformation will be carried out as needed to better meet the normality assumption of t-tests.
Time frame: Baseline to day 57
Adverse events
Number of participants experiencing treatment-related adverse events (AE), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Baseline until 90 day after the last dose of study treatment.
Immunologic effects of FWG (Immune Correlates): distribution of mononuclear cell subsets
Percentage of mononuclear cell subsets in peripheral blood mononuclear cells (PBMC) by a multi-parameter fluorescence-activated cell sorting (FACS).
Time frame: Baseline to day 57
Immunologic effects of FWG (Immune Correlates): assay of T cell proliferation, cytokine production and cytotoxic lymphocyte (CTL) activity
CTL activity will be assessed by using ELISpot Assay to measure percentage of IFN-gamma producing cluster of differentiation 8 (CD8)+T cells as a percentage of peripheral blood mononuclear cells (PBMC).
Time frame: Baseline to day 57
Immunologic effects of FWG (Immune Correlates): T-reg cell function
Percentage change of interleukin-10 (IL-10), IL-4, transforming growth factor β (TGF-β), IL-2, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by multi-parameter fluorescence-activated cell sorting (FACS) analyses from isolated cluster of differentiation (CD)4+CD25+ FoxP3+T cells
Time frame: Baseline to day 57
Immunologic effects of FWG (Immune Correlates): serum cytokines analysis
Percentage change in cytokines and growth factors (including interleukin-1 \[IL-1\], IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, tumor necrosis factor \[TNF\], INF-γ, transforming growth factor-beta \[TGF-beta\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\], platelet-derived growth factor \[PDGF\], and vascular endothelial growth factor \[VEGF\]) in the serum of patients using Luminex assay for immunologic analytes.
Time frame: Baseline to day 57
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