This pilot phase I trial studies how well durvalumab given with or without metformin works in treating participants with head and neck squamous cell carcinoma. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread. Metformin, a drug typically used for the treatment of diabetes, may help to reduce the metabolic activity of cancer cells and of surrounding supportive tissues. It is not yet known whether giving durvalumab with or without metformin may work better in treating participants with head and neck squamous carcinoma.
PRIMARY OBJECTIVES: I. To investigate the combined effect of metformin and durvalumab on the immune tumor microenvironment, specifically with respect to alterations in T cell polarization (Th1/Th2 ratio) and tumor associated macrophage (TAM) (M1/M2 ratio) as measured by cytokine shifts in tumor specimens and peripheral blood. SECONDARY OBJECTIVES: I. To investigate the combined effect of metformin and durvalumab on the metabolic microenvironment, specifically with respect to alterations in immunohistochemical markers of the reverse Warburg effect. II. To further characterize the alterations in intratumoral immune cell populations (effector T cells \[Teff\], regulatory T cells \[Tregs\], tumor associated macrophages \[TAMs\], and myeloid-derived suppressor cells \[MDSC\]). III. To assess changes of the intratumoral immunophenotype and metabolism after exposure to durvalumab and metformin by transcriptome analysis using a ribonucleic acid-sequencing (RNA-seq) transcriptome analysis. IV. To assess the efficacy of combined durvalumab and metformin treatment prior to surgery as determined by radiographic response and immune-related response criteria (irRC). V. To assess the safety and tolerability of the combination of metformin and durvalumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Given PO
Given IV
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Immune cell polarization (Th1/Th2; M1/M2)
The biomarker data will be compared for differences in means (or geometric means) between treatment arms using Student's t-tests on the raw data (or on log-transformed data depending on the degree and nature of skew in the data). Non-parametric alternatives, such as permutation tests, will be considered if the data are not approximately normal for any continuous outcome variables after log-transformation. A similar approach will be used for making pre vs. post treatment comparisons, when necessary, but with paired t-tests or their non-parametric alternatives. The response outcomes will be evaluated between treatment arms by Fisher's exact tests.
Time frame: Up to 6 months
Alterations in immunohistochemical (IHC) markers
Pre- and post-treatment patient tumor samples will be compared. The study will compare data from patients treated with durvalumab and metformin to patients treated with Durvalumab alone and to patients from our own historical controls of head and neck squamous carcinoma (HNSCC), both untreated and treated with metformin monotherapy
Time frame: Up to 6 months
Alterations in intratumoral immune cell populations
The biomarker data will be compared for differences in means (or geometric means) between treatment arms using Student's t-tests on the raw data (or on log-transformed data depending on the degree and nature of skew in the data). Non-parametric alternatives, such as permutation tests, will be considered if the data are not approximately normal for any continuous outcome variables after log-transformation. A similar approach will be used for making pre vs. post treatment comparisons, when necessary, but with paired t-tests or their non-parametric alternatives.
Time frame: Up to 6 months
Changes of the intratumoral immunophenotype and metabolism after exposure to durvalumab and metformin
The biomarker data will be compared for differences in means (or geometric means) between treatment arms using Student's t-tests on the raw data (or on log-transformed data depending on the degree and nature of skew in the data). Non-parametric alternatives, such as permutation tests, will be considered if the data are not approximately normal for any continuous outcome variables after log-transformation. A similar approach will be used for making pre vs. post treatment comparisons, when necessary, but with paired t-tests or their non-parametric alternatives.
Time frame: Baseline up to 6 months
Tumor size as measured by immune-related response criteria (irRC)
The biomarker data will be compared for differences in means (or geometric means) between treatment arms using Student's t-tests on the raw data (or on log-transformed data depending on the degree and nature of skew in the data). Non-parametric alternatives, such as permutation tests, will be considered if the data are not approximately normal for any continuous outcome variables after log-transformation. A similar approach will be used for making pre vs. post treatment comparisons, when necessary, but with paired t-tests or their non-parametric alternatives. The response outcomes will be evaluated between treatment arms by Fisher's exact tests.
Time frame: Up to 4 weeks post-treatment
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