Diarrhea, Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DIETARY_SUPPLEMENTMicronutrient-Fortified Probiotic Yogurt
Receive Activia yogurt
DRUGVEGF-TKI
Must be received as standard of care chemotherapy
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response | Up to 3 years | 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 | Up to 13 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 36 months | 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. |
| Clinical Benefit Rate | Up to 6 months | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Probiotic Yogurt Supplement) Patients receive 4 oz. probiotic supplement Activia yogurt bid during weeks 2-13 and refrain from taking/consuming other probiotic supplements.
Micronutrient-Fortified Probiotic Yogurt: Receive Activia yogurt
VEGF-TKI: Must be received as standard of care chemotherapy | 10 |
| 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.
Laboratory Biomarker Analysis: Correlative studies
VEGF-TKI: Must be received as standard of care chemotherapy | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Arm II (no Intervention) | Total | Arm I (Probiotic Yogurt Supplement) |
|---|---|---|---|
| Age, Continuous | 67.5 years | 67.5 years | 67.0 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 10 participants | 20 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 10 | 6 / 10 |
| other Total, other adverse events | 9 / 10 | 8 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: Up to 13 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Probiotic Yogurt Supplement) | Number of Participants With Diarrhea | 4 Participants |
| Arm II (no Intervention) | Number of Participants With Diarrhea | 4 Participants |
p-value: 1Fisher Exact
Primary
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
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Probiotic Yogurt Supplement) | Number of Participants With Overall Response | 2 Participants |
| Arm II (no Intervention) | Number of Participants With Overall Response | 1 Participants |
Secondary
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
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Probiotic Yogurt Supplement) | Clinical Benefit Rate | 70 percentage of participants |
| Arm II (no Intervention) | Clinical Benefit Rate | 80 percentage of participants |
Secondary
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.
Time frame: Up to 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Probiotic Yogurt Supplement) | Progression-free Survival (PFS) | 6.2 Months |
| Arm II (no Intervention) | Progression-free Survival (PFS) | 13.8 Months |
p-value: 0.077Log Rank