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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

Primary Purpose

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

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Micronutrient-Fortified Probiotic Yogurt
VEGF-TKI
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Diarrhea

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (probiotic yogurt supplement)

Arm II (no intervention)

Arm Description

Patients receive probiotic supplement Activia yogurt QD during weeks 2-13 of VEGF-TKI treatment.

Patients avoid any intake of yogurt or yogurt-containing foods and refrain from taking/consuming other probiotic supplements for 3 months.

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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
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.

Full Information

First Posted
July 27, 2016
Last Updated
March 28, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02944617
Brief Title
Probiotic Yogurt Supplement in Reducing Diarrhea in Patients With Metastatic Kidney Cancer Being Treated With Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitor
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 Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 11, 2016 (Actual)
Primary Completion Date
December 19, 2021 (Actual)
Study Completion Date
December 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 (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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diarrhea, Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (probiotic yogurt supplement)
Arm Type
Experimental
Arm Description
Patients receive probiotic supplement Activia yogurt QD during weeks 2-13 of VEGF-TKI treatment.
Arm Title
Arm II (no intervention)
Arm Type
Active Comparator
Arm Description
Patients avoid any intake of yogurt or yogurt-containing foods and refrain from taking/consuming other probiotic supplements for 3 months.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Dietary Supplement
Intervention Name(s)
Micronutrient-Fortified Probiotic Yogurt
Intervention Description
Receive Activia yogurt
Intervention Type
Drug
Intervention Name(s)
VEGF-TKI
Intervention Description
Must be received as standard of care chemotherapy
Primary Outcome Measure Information:
Title
Number of Participants With Overall Response
Description
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
Time Frame
Up to 3 years
Title
Number of Participants With Diarrhea
Description
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.
Time Frame
Up to 13 weeks
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate
Description
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
Time Frame
Up to 6 months
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
Up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sumanta Pal
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33135866
Citation
Dizman N, Hsu J, Bergerot PG, Gillece JD, Folkerts M, Reining L, Trent J, Highlander SK, Pal SK. Randomized trial assessing impact of probiotic supplementation on gut microbiome and clinical outcome from targeted therapy in metastatic renal cell carcinoma. Cancer Med. 2021 Jan;10(1):79-86. doi: 10.1002/cam4.3569. Epub 2020 Nov 1.
Results Reference
derived

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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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