This phase II trial compares the effect of adding a Live Biotherapeutic Product called CBM588 to pembrolizumab versus pembrolizumab alone in preventing return of disease (recurrence) after surgery for patients with renal cell cancer. Pembrolizumab is an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab is approved for the treatment of renal cell cancer after surgery. Research has shown that changes to the composition of the healthy bacteria in the body (the microbiome), may improve a patient's response to treatment with immunotherapy. CBM588, a Live Biotherapeutic Product (LBP) containing a bacteria called Clostridium butyricum, has been shown to improve outcomes in patients treated with immunotherapy for other types of cancer. Adding CBM588 to treatment with pembrolizumab after surgery may cause changes in the microbiome that improve patient response to treatment and reduce disease recurrence, compared to pembrolizumab alone.
PRIMARY OBJECTIVE: I. To determine if the Clostridium butyricum CBM588 strain (CBM588) increases interleukin (IL)-12 production in patients with high-risk, resected renal cell carcinoma (RCC) receiving pembrolizumab. SECONDARY OBJECTIVES: I. To determine if CBM588 improves recurrence-free survival (RFS) in patients with high-risk, resected renal cell carcinoma (RCC) receiving pembrolizumab. II. To determine if CBM588 improves overall survival (OS) in patients with high-risk, resected renal cell carcinoma (RCC) receiving pembrolizumab. III. To characterize global changes in stool microbiome profile in patients with high-risk, resected RCC receiving pembrolizumab with or without CBM588. IV. To characterize changes in circulating cytokine and immune cell populations in patients with high-risk, resected RCC receiving pembrolizumab with or without CBM588. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive CBM588 orally (PO) twice daily (BID) on days 1-21 or days 1-42 of each cycle and pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and computed tomography (CT) throughout the study. ARM 2: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Undergo collection of blood samples
Given PO
Undergo CT
Given IV
City of Hope Medical Center
Duarte, California, United States
City of Hope at Irvine Lennar
Irvine, California, United States
Change in interleukin (IL)-12 levels
A two-sample t-test will be used to test the difference in the changes in IL-12 production for the two treatment arms. A Wilcoxon rank-sum test will be used if the changes are not normally distributed (p\< 0.05 by a Shapiro-Wilks test).
Time frame: Baseline to week 12
Recurrence-free survival (RFS)
RFS will be estimated by the Kaplan-Meier method. Median RFS and landmark RFS rates (e.g., 1-year and 2-year RFS) will be calculated with confidence intervals. Log-rank test will be used to compare the distribution between groups. Cox proportional hazards model will be used to estimate hazard ratios with 95% confidence intervals.
Time frame: From randomization to disease recurrence or death, assessed up to 1 year
Overall survival (OS)
OS will be estimated by the Kaplan-Meier method. Median OS and landmark OS rates (e.g., 1-year and 2-year OS) will be calculated with confidence intervals. Log-rank test will be used to compare the distribution between groups. Cox proportional hazards model will be used to estimate hazard ratios with 95% confidence intervals.
Time frame: From randomization to death from any cause, assessed up to 1 year
Shannon diversity index
A comparison of the Shannon diversity index (a measure of microbial diversity) from baseline to week 12 will be conducted.
Time frame: Baseline to week 12
Proportion of circulating regulatory T cells (Tregs)
Will estimate the proportion of Tregs in the blood.
Time frame: Baseline to week 12
Proportion of circulating myeloid derived suppressor cells (MDSCs)
Will estimate the proportion of MDSCs in the blood.
Time frame: Baseline to week 12
IL-6, IL-8 and other cytokines/chemokines
Will compare IL-6, IL-8 and other cytokines/chemokines.
Time frame: Baseline to week 12
Incidence of toxicities
Toxicities such as diarrhea and nausea will be assessed using Common Terminology Criteria for Adverse Events version 5 criteria. Will perform statistical analysis to compare the rates of all grade and grade ≥ 3 treatment related adverse events.
Time frame: Up to 30 days after last dose
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