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

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the probiotic VSL#3® 450B can reduce colon inflammation and diarrhea in cancer patients receiving immunotherapy. Immunotherapy helps the immune system fight cancer but can sometimes cause these side effects. Participants take the probiotic before and during immunotherapy sessions. Individuals diagnosed with solid tumor cancer who are about to start or have just started immunotherapy might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to understanding how probiotics might alleviate cancer treatment side effects.

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 prior data suggests that VSL#3® 450B is safe for cancer patients on immunotherapy?

Research has shown that VSL#3® 450B, a type of probiotic, is under study for its potential to reduce gut inflammation caused by certain cancer treatments. This inflammation, known as immune checkpoint inhibitor-induced colitis, can affect up to 45% of patients receiving immunotherapy.

Studies have found that probiotics like VSL#3® 450B are usually well-tolerated, meaning they rarely cause problems. Past research has reported few serious side effects, suggesting that VSL#3® 450B might be safe to use alongside cancer treatments to help prevent uncomfortable gut issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard cancer treatments that primarily focus on targeting cancer cells directly, VSL#3® 450B is a probiotic designed to support the gut microbiome of patients undergoing immunotherapy. This probiotic consists of live freeze-dried lactic acid bacteria, which may enhance the body's immune response by promoting a healthier gut environment. Researchers are excited because this approach could potentially improve the effectiveness of immunotherapy and reduce its side effects, offering a complementary strategy to enhance cancer treatment outcomes.

What evidence suggests that VSL#3® 450B might be an effective treatment for immune checkpoint inhibitor induced colitis?

Research has shown that taking probiotics like VSL#3® 450B might help reduce colitis, a side effect of cancer treatment characterized by colon inflammation. This side effect can affect up to 45% of cancer patients receiving immunotherapy. In this trial, participants will receive VSL#3® 450B. Some studies suggest that it can lower the risk of developing colitis. The probiotics work by balancing gut bacteria, which may prevent inflammation. While more research is needed, early results are promising for those undergoing cancer treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Saranya Chumsri, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 or receiving the next cycle of 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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Citations

1. mayo.edu mayo.edu/research/clinical-trials/cls-20569428

Probiotics Preventing Immune Checkpoint Inhibitor ... This is a prospective, pilot, single arm study to evaluate the incidence of IIC in patients with solid malignancies receiving VSL#3 and ICIs.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05551

Probiotics for the Prevention of Immunotherapy Induced ... Taking probiotics VSL#3® 450B may reduce the chances of developing immune checkpoint inhibitor induced colitis in patients receiving immunotherapy.

3. trialx.com trialx.com/clinical-trials/listings/305772/probiotics-for-the-prevention-of-immunotherapy-induced-colitis-in-patients-receiving-immunotherapy/

Probiotics for the Prevention of Immunotherapy Induced ... Taking probiotics VSL#3® 450B may reduce the chances of developing immune checkpoint inhibitor induced colitis in patients receiving ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1471491424002661

Immune-mediated colitis after immune checkpoint inhibitor ... Immune checkpoint inhibitors (ICIs) have led to improved outcome in patients with various types of cancer. Due to inhibition of physiological ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/17562848251358174

Management of gastrointestinal adverse effects in immune- ... Notably, the oral intake of the probiotic VSL#3® 450B for reducing the incidence of ICI-induced colitis in human patients (NCT06508034) is ...