Immune Checkpoint Blockade + Prebiotic Diet for Melanoma

Overseen By Jennifer McQuade, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Neoadjuvant Ipi/Nivo

Must not be taking: Steroids, Antibiotics, Supplements

Disqualifiers: Uveal melanoma, Inflammatory bowel disease, Insulin-dependent diabetes, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking steroids over a certain dose or regularly taking supplements with prebiotics, fiber, or probiotics unless you can stop them for the study.

What data supports the effectiveness of the treatment Neoadjuvant Immune Checkpoint Blockade, Prebiotic Xnack Packouts for melanoma?

Research shows that certain gut bacteria, like Bifidobacterium, can enhance the effectiveness of immune checkpoint therapies, which are treatments that help the immune system fight cancer. Additionally, prebiotics, which are foods that feed good bacteria in the gut, have been shown to boost anti-tumor immune responses and improve the effectiveness of cancer treatments in mice. ^{1 2 3 4 5}

Is the combination of immune checkpoint blockade and a prebiotic diet safe for humans?

Research suggests that immune checkpoint blockade can cause immune-related adverse events (side effects where the immune system attacks normal cells), and the gut microbiome (bacteria in the digestive system) may predict these events. Prebiotics, which help beneficial gut bacteria grow, have shown potential in enhancing anti-tumor immunity in mice, but specific safety data for humans is not detailed in the available studies. ^{1 2 3 6 7}

How does the treatment Prebiotic Xnack Packouts differ from other treatments for melanoma?

Prebiotic Xnack Packouts is unique because it combines immune checkpoint blockade with a prebiotic diet to enhance the body's immune response against melanoma. This approach leverages the gut microbiota to boost anti-tumor immunity, which is different from traditional treatments that do not focus on modifying gut bacteria to improve cancer therapy outcomes. ^{1 2 3 4 8}

What is the purpose of this trial?

To Determine the feasibility, compliance and adherence to PreFED intervention in resectable melanoma patients initiating neoadjuvant Ipi/Nivo.

Research Team

Jennifer McQuade

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals with melanoma that can be surgically removed. They are looking to see if people will follow a special diet containing Prebiotic Xnack Packouts while also receiving immune checkpoint blockade therapy.

Inclusion Criteria

Body mass index (BMI) 18.5-45 kg/m2

Measurable disease per RECIST 1.1

English-speaking

Exclusion Criteria

I am currently taking more than 10 mg/day of Prednisone or its equivalent.

Current smoker or heavy drinker (defined as >14 drinks per week) or current illicit drug use

I cannot or do not want to follow the study's required procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant immune checkpoint blockade therapy combined with a prebiotic food-enriched dietary intervention

2 cycles

Surgery

Participants undergo surgery to assess systemic and tumor immunity

Maintenance

Participants continue with dietary intervention and immune checkpoint blockade to assess long-term effects

Up to 2 years

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment

Up to 2 years

Treatment Details

Interventions

• Neoadjuvant Immune Checkpoint Blockade
• Prebiotic Xnack Packouts

Trial Overview The study tests whether adding a prebiotic-enriched diet (PreFED) improves the effectiveness of neoadjuvant Ipi/Nivo, an immunotherapy treatment, in patients with resectable melanoma.

Participant Groups

Group I: Prebiotic food-enriched diet (PreFED) Experimental Treatment 1 Intervention

Participants will identified from the clinic schedules and/or referred from participant's treating oncologists.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study comparing melanoma growth in mice with different gut microbiota, the presence of Bifidobacterium was linked to improved antitumor immunity, suggesting that gut bacteria can influence immune responses to tumors.

Oral administration of Bifidobacterium alone was as effective as PD-L1-specific antibody therapy in controlling tumor growth, and when combined, they nearly eliminated tumor outgrowth, indicating that modifying the microbiota could enhance cancer immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Sivan, A., Corrales, L., Hubert, N., et al.[2022]

Prebiotics like inulin and mucin can enhance anti-tumor immune responses and inhibit melanoma growth in mice, but the presence of gut microbiota is essential for this effect, as shown by the lack of tumor inhibition in germ-free mice.

Inulin specifically not only limits tumor growth in various cancer models but also improves the effectiveness of a MEK inhibitor and helps delay drug resistance, highlighting its potential as a therapeutic strategy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth. Li, Y., Elmén, L., Segota, I., et al.[2022]

A diet high in fiber is associated with better responses to checkpoint inhibitors in cancer treatment, suggesting that nutrition may play a role in enhancing the effectiveness of immunotherapy.

The study indicates that avoiding commercial probiotics may also contribute to improved outcomes when using checkpoint inhibitors, highlighting the importance of gut health in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Commercial Probiotic Use and a High Fiber Diet Improves Immunotherapy Response. [2022]

In a study of 128 melanoma patients undergoing immune checkpoint blockade (ICB) treatment, higher dietary fiber intake was linked to significantly improved progression-free survival, especially in patients not using probiotics.

Preclinical models supported these findings, showing that a low-fiber diet or probiotic use impaired the response to anti-PD-1 therapy, indicating that diet can influence the effectiveness of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Spencer, CN., McQuade, JL., Gopalakrishnan, V., et al.[2023]

The gut microbiome can predict the risk of developing immune-related adverse events (irAEs) in melanoma patients undergoing immune checkpoint blockade (ICB) therapy, with two distinct bacterial community clusters identified that show a nearly 7-fold difference in risk.

Specific bacterial strains, such as Bacteroides dorei in the high-risk group and Bacteroides vulgatus in the low-risk group, were linked to the likelihood of developing irAEs, suggesting that the gut microbiome composition may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma. Usyk, M., Pandey, A., Hayes, RB., et al.[2022]

A study of 103 melanoma patients from Australia and the Netherlands found that gut microbiota composition significantly influences the effectiveness of immune checkpoint inhibitors (ICIs), with better responses linked to Ruminococcaceae-dominated microbiomes.

Dietary factors, such as lower fiber and omega-3 fatty acid intake, along with higher levels of systemic inflammation (C-reactive protein), were associated with poorer responses to ICIs, highlighting the importance of diet and inflammation in cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome. Simpson, RC., Shanahan, ER., Batten, M., et al.[2023]

Metastatic melanoma patients who achieved a complete and sustained response to immunotherapy showed significant differences in their gut microbiome composition, particularly with higher diversity and specific bacterial abundances, compared to those with early responses.

These late responders also had distinct dietary habits, including lower protein and sugar intake and higher flavonoid consumption, suggesting that both microbiome and diet may play a role in enhancing the effectiveness of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy. Golčić, M., Simetić, L., Herceg, D., et al.[2023]

References

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

Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. [2022]

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

Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth. [2022]

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

Low Commercial Probiotic Use and a High Fiber Diet Improves Immunotherapy Response. [2022]

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

A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota. [2023]

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

Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma. [2022]

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

Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy. [2023]