Probiotic Yogurt Supplement in Reducing Diarrhea in Patients With Metastatic Kidney Cancer Being Treated With Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitor

Study Overview
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Brief Summary
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This randomized clinical trial studies how well probiotic yogurt supplement works in reducing diarrhea in patients with kidney cancer that has spread from the primary site to other places in the body (metastatic) and that are being treated with vascular endothelial growth factor-tyrosine kinase inhibitor therapy. Studying samples of blood and stool from patients who eat probiotic yogurt and those who avoid probiotic yogurt may help doctors plan better treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if adding Activia yogurt (containing Bifidobacterium lactis DN-173 010) to the diet of patients with metastatic renal cell carcinoma (mRCC) increases the level of Bifidobacterium spp in stool. SECONDARY OBJECTIVES: I. To determine if Activia reduces the incidence of diarrhea for mRCC patients treated with vascular endothelial growth factor - tyrosine kinase inhibitor (VEGF-TKI) therapy. II. To compare pre-treatment levels of circulating T regulatory (Treg) cells and levels of peripheral signal transducers and activators of transcription 3 (STAT3) in patients with and without diarrhea with VEGF-TKI therapy, and correlate with Bifidobacterium, other bacteria, and Activia. III. To determine if patients with the diarrhea in mRCC patients treated with VEGF-TKI therapy have a lower baseline of Bifidobacterium spp. IV. To assess the change in global stool bacteriomic profile of patients receiving therapy with VEGF-TKI therapy with or without Activia. V. To better assess the feasibility of stool collection and bacteriomic profiling. VI. To explore association between psychosocial symptoms (anxiety and depression) and bacteriomic profile and gastrointestinal toxicity in mRCC patients receiving VEGF-TKI therapy therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive probiotic supplement Activia yogurt twice daily (QD) during weeks 2-13 of VEGF-TKI treatment. ARM II: Patients avoid any intake of yogurt or yogurt-containing foods and refrain from taking/consuming other probiotic supplements for 3 months.

Official Title
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Assessment of the Role of Bifidobacterium-Containing Food Supplement Activia™ and Bacteriomic Profiling and Other Biomarkers Associated With Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor (VEGF-TKI)-Induced Diarrhea in Patients With Metastatic Renal Cell Carcinoma (mRCC)

Conditions
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Diarrhea, Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Dietary Supplement: Micronutrient-Fortified Probiotic Yogurt
* Drug: VEGF-TKI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or pathologically verified diagnosis of renal cell carcinoma (RCC) Diagnosis of RCC that is defined as metastatic by standard criteria (American Joint Committee on Cancer [AJCC] 7th edition, 2010) Planned treatment with any VEGF-TKI, treatment has not yet begun Ability to understand and the willingness to sign a written informed consent Ability to read and write English Documented consent to participation to include the following study specific procedures: Be able to provide up to six serial stool collections at home and deliver to FedEx location that day as per standard operating procedure Have three 10-ml blood samples taken during a routine clinic visit To not take probiotic supplements except as oriented If randomized to the probiotic-supplemented group (the yogurt-based supplement Activia), be willing to comply with daily intake and record this intake as a component of a dietary log; the patient will be asked not to take any yogurt or yogurt-containing foods beyond this If randomized to the probiotic-restricted group, agree not to consume yogurt or yogurt-containing foods Maintain a dietary log and stool frequency log Exclusion Criteria: Patients with a known intolerance to lactose or other constituents of Activia Patients with irritable bowel syndrome, Crohn's disease, or other clinically significant gastrointestinal (GI) related condition that might confound the VEGF-TKI-related-diarrhea endpoint Patients taking antibiotics or who plan to begin taking antibiotics Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures (including compliance issues related to feasibility/logistics)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (probiotic yogurt supplement)<br>Patients receive probiotic supplement Activia yogurt QD during weeks 2-13 of VEGF-TKI treatment. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Dietary Supplement: Micronutrient-Fortified Probiotic Yogurt<br>* Receive Activia yogurt<br>Drug: VEGF-TKI<br>* Must be received as standard of care chemotherapy<br>|
| Active Comparator: Arm II (no intervention)<br>Patients avoid any intake of yogurt or yogurt-containing foods and refrain from taking/consuming other probiotic supplements for 3 months. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: VEGF-TKI<br>* Must be received as standard of care chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | Up to 3 years | 
| Number of Participants With Diarrhea | The rate of all grade diarrhea as graded by the Common Terminology Criteria for Adverse Events version 4.0 will be compared in the patients who receive the dietary supplement and those who do not. A Fisher's exact test with a 0.050 one-sided significance level will be used. | Up to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR; Stable disease (SD): Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). Clinical Benefit Rate (CBR) = CR + PR + SD at 6 months | Up to 6 months | 
| Progression-free Survival (PFS) | Estimated using the product-limit method of Kaplan and Meier. Failure defined as disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Up to 36 months |