Probiotics for Cancer Patients on Immunotherapy

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must be taking: Immunotherapy

Must not be taking: Antibiotics, Steroids

Disqualifiers: IBD, Chronic diarrhea, Celiac, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require prolonged antibiotic therapy or have used systemic steroids in the last 90 days.

What data supports the effectiveness of the treatment VSL#3® 450B for cancer patients on immunotherapy?

VSL#3, a probiotic mix, has shown benefits in managing conditions like irritable bowel syndrome and ulcerative colitis, suggesting it may help improve gut health. While not directly related to cancer, these benefits indicate potential for supporting overall health in cancer patients on immunotherapy. ^{1 2 3 4 5}

Is VSL#3 safe for use in humans?

VSL#3 has been generally well tolerated in clinical trials for conditions like ulcerative colitis and pouchitis, with no major safety concerns reported. However, differences in manufacturing processes can affect the product, and it's important to ensure the specific version being used has been tested for safety. ^{2 3 5 6 7}

How do probiotics differ from other treatments for cancer patients on immunotherapy?

Probiotics are unique because they aim to support cancer treatment by modulating the gut microbiome, which can influence the immune system's response to cancer. Unlike traditional cancer treatments, probiotics are taken orally and are not yet FDA-approved for use with immunotherapy, but they are being explored as a potential 'living adjuvant' to enhance the effectiveness of immunotherapy. ^{2 5 8 9 10}

Research Team

Saranya Chumsri, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with inflammatory bowel disease or cancer who are undergoing immunotherapy. It aims to see if taking the probiotic VSL#3® can prevent colitis, a common side effect of their treatment. Participants must meet certain health criteria to join.

Inclusion Criteria

I will be starting treatment with immune checkpoint inhibitors.

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

Exclusion Criteria

I have a history of short gut syndrome or problems with how my intestines move food.

I experienced a serious side effect from a fecal transplant.

I have had a fecal transplant in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Pre-Treatment

Participants receive VSL#3® 450B at least 3 days prior or 1-2 weeks prior to starting standard care ICIs

1-2 weeks

Treatment

Participants continue receiving VSL#3® 450B for 12 weeks while undergoing standard care ICIs

12 weeks

Regular visits for stool and blood sample collections

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Follow-up visits at 30 days and 1 year post-treatment

Treatment Details

Interventions

• VSL#3® 450B

Trial Overview The study tests whether the over-the-counter probiotic VSL#3® helps prevent colon inflammation and diarrhea in patients treated with immunotherapy. The trial involves biospecimen collection, questionnaires, and administering the live freeze-dried lactic acid bacteria probiotic.

Participant Groups

Group I: Treatment (VSL#3® 450B) Experimental Treatment 3 Interventions

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 ICIs and then continue for 12 weeks. Patients also undergo stool and blood sample collections on study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

In a study of 144 patients with relapsing ulcerative colitis, VSL#3 probiotic supplementation significantly reduced disease activity scores compared to placebo, with 63.1% of patients in the VSL#3 group achieving a 50% or more decrease in UCDAI scores.

VSL#3 was found to be safe, with only mild side effects reported in 11.2% of patients, and it showed potential benefits in improving rectal bleeding and inducing remission, although these results did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Tursi, A., Brandimarte, G., Papa, A., et al.[2022]

The new formulation of VSL#3 produced in Italy contains 130-150% more dead bacteria compared to the original product from the USA, raising safety concerns due to potential adverse effects associated with dead microbes.

In vitro tests showed that the original VSL#3 was more effective in inhibiting tumor cell growth and promoting cell death compared to the newfound formulation, highlighting the importance of production conditions for probiotics intended for serious health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production Conditions Affect the In Vitro Anti-Tumoral Effects of a High Concentration Multi-Strain Probiotic Preparation. Cinque, B., La Torre, C., Lombardi, F., et al.[2022]

In a systematic review of five studies involving 441 patients, VSL#3 probiotic was found to significantly improve remission rates in mild to moderately active ulcerative colitis, achieving a remission rate of 49.4%.

Patients treated with VSL#3 showed a higher response rate (53.4%) compared to placebo (29.3%), with no serious side effects reported, indicating that VSL#3 is a safe and effective addition to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis. Mardini, HE., Grigorian, AY.[2018]

In a study involving IL-10 gene-deficient mice, VSL#3 was effective as a primary therapy for colitis, improving colonic function and reducing inflammation markers like tumor necrosis factor alpha.

VSL#3 enhanced epithelial barrier function and resistance to infections in laboratory studies, suggesting its beneficial mechanisms may involve secreted factors that strengthen gut defenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Madsen, K., Cornish, A., Soper, P., et al.[2019]

A meta-analysis of 5 randomized controlled trials involving 243 patients found that VSL#3 did not show significant improvements in abdominal pain, bloating, stool consistency, or quality of life for individuals with irritable bowel syndrome (IBS).

There was a trend suggesting that VSL#3 might improve overall response rates, but the evidence was not strong, and the authors recommend larger studies to better assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis: Efficacy of patented probiotic, VSL#3, in irritable bowel syndrome. Connell, M., Shin, A., James-Stevenson, T., et al.[2023]

In a review of three double-blind, randomized, placebo-controlled trials involving 120 patients, VSL#3® was found to be safe and well-tolerated, with no significant difference in adverse events compared to placebo.

Out of the patients analyzed, 64.1% in the VSL#3® group and 64.5% in the placebo group reported at least one adverse event, indicating that the probiotic does not increase the risk of adverse effects compared to a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials. Panetta, V., Bacchieri, A., Papetti, S., et al.[2022]

VSL#3, a high-concentration probiotic containing eight bacterial strains, shows promise in treating mild to moderate ulcerative colitis and maintaining remission, based on data from noncomparative trials.

A randomized trial indicated that VSL#3 combined with low-dose balsalazide is more effective than standard treatments for acute ulcerative colitis, and it is also effective in preventing and managing pouchitis, with good tolerability reported in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Chapman, TM., Plosker, GL., Figgitt, DP.[2018]

In a survey of 499 cancer patients, 28.5% reported using probiotics, primarily based on recommendations from healthcare professionals, highlighting a significant interest in these supplements during cancer treatment.

Despite the low incidence of negative side effects (only 8.5% reported any), 86.6% of patients were unaware of potential risks associated with probiotic use, indicating a need for oncologists to better inform patients about the safety and implications of probiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic Survey in Cancer Patients Treated in the Outpatient Department in a Comprehensive Cancer Center. Ciernikova, S., Mego, M., Semanova, M., et al.[2018]

The gut microbiome plays a crucial role in cancer treatment, influencing how well patients respond to immunotherapy, with differences noted between those who are sensitive and resistant to treatment.

Research is ongoing to identify specific beneficial or harmful bacterial strains in the gut, and strategies like dietary fiber, prebiotics, and fecal microbiota transplantation may improve immune responses in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy. Singh, A., Alexander, SG., Martin, S.[2023]

Probiotics can help maintain a balanced gut microbiome, which is crucial for preventing pro-inflammatory responses that may lead to diseases like cancer.

Research indicates that certain probiotic strains can not only prevent cancer but also support treatment during chemotherapy by modulating the immune response and intestinal microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Probiotics in Cancer Prevention. Śliżewska, K., Markowiak-Kopeć, P., Śliżewska, W.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Production Conditions Affect the In Vitro Anti-Tumoral Effects of a High Concentration Multi-Strain Probiotic Preparation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Probiotic bacteria enhance murine and human intestinal epithelial barrier function. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis: Efficacy of patented probiotic, VSL#3, in irritable bowel syndrome. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Probiotic Survey in Cancer Patients Treated in the Outpatient Department in a Comprehensive Cancer Center. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Probiotics in Cancer Prevention. [2021]