This phase I trial studies how well CBM588 works when given together with nivolumab and ipilimumab in treating patients with kidney cancer that is stage IV or has spread to other places in the body (advanced). CBM588 is a probiotic that may help to increase the effect of immunotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CBM588, nivolumab, and ipilimumab may work better in treating patients with kidney cancer.
PRIMARY OBJECTIVES: I. To determine the effect of clostridium butyricum CBM 588 probiotic strain (CBM588) (in combination with nivolumab/ipilimumab) on the gut microbiome in patients with metastatic renal cell carcinoma (mRCC). SECONDARY OBJECTIVES: I. To evaluate the effect of CBM588 on the clinical efficacy of the nivolumab/ipilimumab combination. II. To assess the effect of CBM588 on systemic immunomodulation of the nivolumab/ipilimumab combination in patients with mRCC. III. To assess the effect of CBM588 on toxicities such as diarrhea and nausea using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 criteria with the nivolumab/ipilimumab combination in patients with mRCC. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive clostridium butyricum CBM 588 probiotic strain orally (PO) twice daily (BID), nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588 probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and periodically thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
City of Hope Medical Center
Duarte, California, United States
Change in Bifidobacterium composition of stool
Will be assessed for patients on both arms.
Time frame: Baseline up to week 12
Change in Shannon index
Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.
Time frame: Baseline up to week 12
Best overall response
Will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST). The association between treatment arm and overall response as per RECIST criteria (response observed versus \[vs\] not observed) will be examined using Fisher's exact test.
Time frame: Up to 2 years
Progression-free survival (PFS)
The difference in progression free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median PFS time for each of the two arms will be reported and Cox proportional hazards model will be used to estimate the hazard ratio and its confidence interval.
Time frame: From enrollment to progression, assessed up to 2 years
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