This phase I trial tests the safety, side effects, and best dose of camu camu when used in combination with nivolumab and ipilimumab in treating patients with kidney cancer that has spread to other places in the body. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Camu camu is a prebiotic that may have a beneficial effect on the immune system. Giving camu camu in combination with nivolumab and ipilimumab may kill more tumor cells than nivolumab and ipilimumab alone in patients with metastatic kidney cancer.
PRIMARY OBJECTIVE: I. To determine the effect of camu camu in combination with nivolumab/ipilimumab on Ruminococcus abundance in stool samples of patients with metastatic renal cell carcinoma (mRCC). SECONDARY OBJECTIVES: I. To evaluate the effect of camu camu on the clinical efficacy of the nivolumab/ipilimumab combination. II. To determine the effect of camu camu on systemic immunodulation of the nivolumab/ipilimumab combination in patients with mRCC. III. To describe the toxicity and safety profile of the use of camu camu in combination with nivolumab/ipilimumab. IV. To determine the effect of camu camu on gut microbiome diversity and function. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo computed tomography (CT) and/or bone scan and/or magnetic resonance imaging (MRI) on trial. ARM 2: Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu orally (PO) once a day (QD) continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial. After completion of study treatment, patients are followed up every 12 weeks until time of death or formal withdrawal from the study, whichever comes first.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Undergo blood and stool sample collection
Undergo bone scan
Undergo CT
Given IV
Undergo MRI
Given PO
Given IV
City of Hope Medical Center
Duarte, California, United States
Abundance of ruminococcus in the stool
Using a two-group t-test with a one-sided type I error of 0.05.
Time frame: From baseline to week 12 of therapy
Best overall response
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Will be examined using Fisher's exact test.
Time frame: Every 12 weeks for up to 3 years
Progression-free survival (PFS)
PFS, assessed as the duration of time from enrollment to progression, with camu camu in combination with nivolumab/ipilimumab vs nivolumab/ipilimumab alone. The difference in progression-free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median progression-free survival 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: Time from enrollment to progression date or date of death, whichever occurs first (Each cycle is 4 weeks)
Incidence of adverse events
Will perform statistical analysis to compare the rates of all grade and grade \>= 3 (per Common Terminology Criteria for Adverse Events version 5) treatment related adverse events between nivolumab/ipilimumab and nivolumab/ipilimumab with camu camu arms.
Time frame: Up to 30 days post-last dose of protocol therapy
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.