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

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ClinicalTrials.gov Identifier: NCT02944617
Recruitment Status : Recruiting
First Posted : October 26, 2016
Last Update Posted : February 11, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
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 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.

Condition or disease Intervention/treatment Phase
Diarrhea Metastatic Renal Cell Cancer Stage IV Renal Cell Cancer Other: Laboratory Biomarker Analysis Dietary Supplement: Micronutrient-Fortified Probiotic Yogurt Drug: VEGF‐TKI Not Applicable

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: 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)
Study Start Date : October 18, 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (probiotic yogurt supplement)
Patients receive probiotic supplement Activia yogurt QD during weeks 2-13 of VEGF‐TKI treatment.
Other: Laboratory Biomarker Analysis
Correlative studies

Dietary Supplement: Micronutrient-Fortified Probiotic Yogurt
Receive Activia yogurt

Drug: VEGF‐TKI
Must be received as standard of care chemotherapy

Active Comparator: Arm II (no intervention)
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
Correlative studies

Drug: VEGF‐TKI
Must be received as standard of care chemotherapy




Primary Outcome Measures :
  1. Change in levels of Bifidobacterium spp assessed in stool samples [ Time Frame: Baseline up to 13 weeks ]
    T-test or Mann-Whitney test will be used to test the difference in change from baseline between patients with or without Activia added to the diet.


Secondary Outcome Measures :
  1. Incidence of diarrhea as graded by the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 13 weeks ]
    The rate of all grade diarrhea will be compared in the patients who receive the dietary supplement and those who do not. The rate of grade 3/4 diarrhea will also be compared between the two groups. A Fisher's exact test with a 0.050 one-sided significance level will be used.

  2. Levels of Bifidobacterium spp [ Time Frame: Baseline ]
    The abundance of Bifidobacterium spp will be compared between diarrhea and non-diarrhea patients and the change of bifidobacteria in patients who subsequently get diarrhea.

  3. Levels of circulating Treg cells assessed in peripheral blood mononuclear cells (PMBCs) [ Time Frame: Up to 13 weeks ]
    An analysis will be carried out to evaluate whether Tregs expression differs in patients who develop diarrhea with vascular endothelial growth factor-tyrosine kinase inhibitor therapy as compared to patients who do not. The distribution of the Treg quantity will be examined and log transformation may be applied if the distribution is skewed, Parametric or non-parametric test will be used to compare Tregs between the diarrhea and non-diarrhea groups, and between the Activia and non-Activia groups.

  4. Levels of peripheral STAT3 assessed in PBMCs [ Time Frame: Up to 13 weeks ]
  5. Change in psychosocial (anxiety and depression) symptoms as measured by the Generalized Anxiety Disorder (GAD)-7 and Patient Health Questionnaire for Depression (PHQ)-9 questionnaires [ Time Frame: Baseline up to 13 weeks ]
    Will explore association with bacteriomic profile and gastrointestinal toxicity in metastatic renal cell carcinoma (mRCC) patients treated with VEGF‐TKI therapy. Will dichotomize the population based on low or high depression (and subsequently low and high anxiety). Using descriptive statistics, will then assess differences in response rates, gastrointestinal toxicity, microbial diversity and immune biomarkers.


Other Outcome Measures:
  1. Bacteriomic profiles [ Time Frame: Up to 2.5 years ]
    The association between the subclusters and phenotypic variables will be studied. Principle coordinate analysis will be used to examine possible correlation between phylum/genus and other phenotypic variables.

  2. Feasibility of stool collection measured by compliance with specimen submission [ Time Frame: Up to 13 weeks ]
  3. Feasibility of bacteriomic profiling measured by viable bacteriomic profile results [ Time Frame: Up to 13 weeks ]
    Reasons for inability to perform analysis will be noted (for instance, insufficient DNA collection)

  4. Operational taxonomic units (OTUs) with summary of bacteriomic profiles [ Time Frame: Up to 2.5 years ]
    The relative abundance of OTUs will be calculated at phylum-, class-, order-genus- and species-level taxa. Weighted and unweighted UniFrac distances between samples will be calculated with a de novo tree constructed from representative sequences defining each OTU. A table of OTU counts will be generated and used in combination with the tree to calculate beta diversity. Principle coordinate analysis will be used to examine possible correlation between phylum/genus and other phenotypic variables.

  5. Short read sequences [ Time Frame: Up to 2.5 years ]
    Quantitative insights into microbial ecology will be used to cluster V5-15S rRna Solexa read for each sample, at the level of 97% nucleotide sequence identity. A closed-reference OUT picking protocol with USEARCH against Greengenes database will be used. Taxonomy will be assigned using RDP classifier 2.4.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02944617


Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Sumanta K. Pal    626-256-4673    spal@coh.org   
Principal Investigator: Sumanta K. Pal         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sumanta Pal City of Hope Medical Center

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT02944617     History of Changes
Other Study ID Numbers: 16088
NCI-2016-01068 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
16088 ( Other Identifier: City of Hope Medical Center )
First Posted: October 26, 2016    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: December 2018

Additional relevant MeSH terms:
Diarrhea
Carcinoma, Renal Cell
Signs and Symptoms, Digestive
Signs and Symptoms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Mitogens
Micronutrients
Trace Elements
Endothelial Growth Factors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs