Clinical trial NCT02944617: 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
Overall status: COMPLETED
Phase: NA
Conditions: Diarrhea
Metastatic Renal Cell Carcinoma
Stage IV Renal Cell Cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-10-26
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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)

Primary outcomes:
measure: Number of Participants With Overall Response
timeFrame: Up to 3 years
measure: Number of Participants With Diarrhea
timeFrame: Up to 13 weeks
Secondary outcomes:
measure: Clinical Benefit Rate
timeFrame: Up to 6 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Sumanta Pal
role: PRINCIPAL_INVESTIGATOR
References:
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.