Probiotics for the Prevention of Immunotherapy Induced Colitis in Patients Receiving Immunotherapy

Probiotics Preventing Immune Checkpoint Inhibitor-Induced Colitis

The clinical trial tests the use of over-the-counter probiotics VSL#3® 450B in patients receiving immunotherapy. Immunotherapy with monoclonal antibodies, helps the body's immune system attack tumor cells, and interferes with the ability of tumor cells to grow and spread. Immunotherapy can also cause an unfortunate side effect of inflammation of the colon and diarrhea, also known as immune checkpoint inhibitor induced colitis. Immune checkpoint inhibitor induced colitis can occur in up to 45% of patients receiving immunotherapy. Taking probiotics VSL#3® 450B may reduce the chances of developing immune checkpoint inhibitor induced colitis in patients receiving immunotherapy.

Study Overview

• Status: Suspended
• Conditions: Malignant Solid Neoplasm
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Dietary supplement: Live Freeze-Dried Lactic Acid Bacteria Probiotic

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) in patients with solid malignancies receiving over-the-counter multi-strain probiotic blend and ICIs in both cohorts: (1) anti-Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) +/- anti-programmed cell death-1 (PD-1)/programmed cell death-1 ligand 1 (PD-L1), and (2) anti-PD-1/PD-L1 +/- chemo.

SECONDARY OBJECTIVES:

I. To evaluate the safety of multi-strain probiotic blend in cancer patients receiving ICIs.

II. To evaluate the clinical outcomes related to IIC, including the incidence of IIC, hospitalization, treatment delays, and administration of immunosuppressants.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in gut microbiome with ICIs and multi-strain probiotic blend.

II. To evaluate changes in immune response with ICIs and multi-strain probiotic blend.

OUTLINE:

Patients receive VSL#3® 450B (live freeze-dried lactic acid bacteria probiotic) orally (PO) once daily (QD) at least 3 days prior or 1-2 weeks prior to starting standard care ICIs or receiving the next cycle of ICIs and then continue for 12 weeks. Patients also undergo stool and blood sample collections on study.

After completion of study treatment, patients are followed up at 30 days and 1 year.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Histologically confirmed solid malignancy

• Will be starting on ICIs or have started ≤ 2 cycles of ICIs

  • For cohort 1: Ipilimumab with or without anti-PD-1/PD-L1 including but not limited to pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, or durvalumab
  • For cohort 2: Anti-PD-1/PD-L1 described above with or without chemotherapy
• Absolute neutrophil count (ANC) ≥ 1000/mm^3
• Platelet count ≥ 75,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Creatinine ≤ 2 x upper limit of normal (ULN)
• Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate transaminase (AST)] ≤ 2 x ULN
• Albumin ≥ 3 g/dL
• Willing and able to provide research stool and blood samples
• Negative serum pregnancy test done ≤ 7 days prior to enrollment, for women of childbearing potential only
• Capable of providing valid informed consent
• Willing to return to enrolling institution for all study visits (blood draws, etc)

Exclusion Criteria:

• Requires prolonged systemic antibiotic therapy for other condition and recent systemic antibiotic within the past 2 weeks
• Fecal microbiota transplant (FMT) within the past 6 months
• FMT with an associated serious adverse event related to the FMT product or procedure
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of over-the-counter probiotics
• Immunocompromised patients including patients known to be HIV positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent Note: Must be off systemic steroids at least 90 days prior to enrollment. However, topical steroids, inhalants or steroid eye drops are permitted
• History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis
• History of chronic diarrhea
• History of celiac disease
• Currently has a colostomy
• Intraabdominal surgery related to gastrointestinal tract within the last 60 days
• Evidence of active, severe colitis
• History of short gut syndrome or motility disorders
• Requires the regular use of medications to manage bowel hypermotility
• Active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (VSL#3® 450B); Patients receive VSL#3® 450B (live freeze-dried lactic acid bacteria probiotic) PO QD at least 3 days prior or 1-2 weeks prior to starting standard care or receiving the next cycle of ICIs and then continue for 12 weeks. Patients also undergo stool and blood sample collections on study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo stool and blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Dietary supplement: Live Freeze-Dried Lactic Acid Bacteria Probiotic; Given PO; Other Names: VSL#3; VSL3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) with VSL#3 and ICIs	Will be evaluated in patients with solid malignancies in 2 cohorts, including 1) anti-CTLA4 ± anti-PD-1/PD-L1, 2) anti-PD-1/PD-L1 ± chemotherapy respectively. Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Will be estimated by the number of patients who had IIC divided by the total number of evaluable patients. Two-sided 90% exact confidence intervals for the true incidence rate will be calculated according to the approach of Clopper and Pearson.	Up to 14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Will be evaluated by the safety profile of multi-strain probiotic blend in cancer patients receiving ICIs. Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize toxicity.	Up to 30 days post treatment
Incidence of hospitalization related to IIC	Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize clinical outcomes related to IIC.	Up to 14 weeks
Incidence of treatment delays related to IIC	Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize clinical outcomes related to IIC.	Up to 14 weeks
Incidence of administration of immunosuppressants related to IIC	Analysis will be performed in all-treated population, defined as any subject enrolled into the study that received at least 3 days of VSL#3 and anti-PD-1/PD-L1. The statistical analyses will be handled in a descriptive manner. Descriptive statistics (frequency table) and histogram will be used to summarize clinical outcomes related to IIC.	Up to 14 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Saranya Chumsri, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling
• Other Study ID Numbers: MC210304 (Other Identifier: Mayo Clinic in Florida); NCI-2024-05551 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 21-012363 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No