Prebiotic Diet + Immunotherapy for Melanoma

Overseen By Jennifer McQuade, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Ipilimumab, Nivolumab

Must not be taking: Steroids, Antibiotics, Prebiotics

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a diet rich in prebiotic foods (which feed beneficial gut bacteria) might assist individuals with a specific type of skin cancer called melanoma that hasn't responded to previous treatments. Participants will follow a diet plan while receiving two cancer medicines, ipilimumab (Yervoy) and nivolumab (Opdivo), both immunotherapy drugs, to evaluate the effectiveness of this combination. The trial targets those with stage III/IV melanoma who have tried certain treatments without success and are willing to consume prebiotic-rich foods. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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, have used antibiotics recently, or regularly take supplements with prebiotics, fiber, or probiotics and are unwilling to stop.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that prebiotic diets are generally safe and easy to manage, with no known serious side effects from adding prebiotic foods. These foods support gut health by nourishing beneficial bacteria.

Studies on ipilimumab and nivolumab, two treatments often used together for melanoma, have shown they can cause side effects. Common side effects include tiredness, skin rash, and diarrhea. Some patients might experience more serious effects, such as inflammation in different parts of the body.

Despite potential side effects, these treatments are widely used and researched. Understanding these effects helps doctors manage and reduce risks. Prospective trial participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard melanoma treatments that often rely solely on medications like ipilimumab and nivolumab, this approach combines these immunotherapies with a prebiotic diet. Researchers are excited because the prebiotic diet aims to enhance the gut microbiome, potentially boosting the immune system's response to the cancer. This unique combination could improve treatment effectiveness by not only attacking the cancer cells directly but also by strengthening the body's natural defenses, offering a new angle in the fight against melanoma.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research shows that a diet high in prebiotic foods and fiber may benefit melanoma patients undergoing immunotherapy. Studies have found that a high-fiber diet can enhance the body's response to immunotherapy by positively affecting the gut microbiome, the community of tiny organisms in the intestines. This change in the gut can help the immune system fight cancer more effectively. Early results suggest that these dietary changes could enhance the effectiveness of treatments like ipilimumab and nivolumab, commonly used for melanoma. In this trial, participants will receive prebiotic food-enriched snacks and supportive nutritional counseling to increase prebiotic foods in their diet, aiming to assist patients who haven't responded to other treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

Jennifer McQuade

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced melanoma, who can eat specific foods and are starting standard care with Ipilimumab/Nivolumab. They should be relatively healthy (ECOG 0 or 1), have measurable disease, and not be on certain medications or diets. Pregnant women, heavy drinkers/smokers, and those with some chronic diseases cannot join.

Inclusion Criteria

English-speaking

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

Measurable disease per RECIST 1.1

Exclusion Criteria

Medical contraindications to the Intervention Diet as determined by the treating physician.

Self-reported major dietary restrictions, including but not limited to relevant food allergies, celiac disease, or diets such as vegan, ketogenic, extended fasting.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a prebiotic food-enriched diet in combination with ipilimumab and nivolumab

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Prebiotic Food-Enriched Diet

Trial Overview The study tests if a special diet rich in prebiotics can improve the gut health of patients whose melanoma didn't respond to previous immune therapies while they receive Ipilimumab/Nivolumab as their usual treatment.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 3 Interventions

Patients receive prebiotic food-enriched snacks and supportive nutritional counseling to increase prebiotic foods in diet.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

A diet-driven microbiome community can enhance the effectiveness of immune checkpoint inhibitors in melanoma patients, potentially improving treatment outcomes.

This research suggests that manipulating the diet to influence the microbiome may help reduce immune-related side effects during neoadjuvant therapy, opening new therapeutic possibilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross communication of diet-microbiome-immune interactions in cancer immunotherapy. Zhou, CB., Fang, JY.[2023]

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]

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]

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]

Camu camu (CC) appears to enhance the effectiveness of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma, as demonstrated by two case studies where patients achieved near complete responses after adding CC to their ICI treatment.

Both patients experienced durable responses for over a year with minimal immune-related adverse events, suggesting that CC may help modulate the gut microbiome to improve cancer treatment outcomes while reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Cases of Durable and Deep Responses to Immune Checkpoint Inhibition-Refractory Metastatic Melanoma after Addition of Camu Camu Prebiotic. Pang, SA., Elkrief, A., Capella, MP., et al.[2023]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06250335

NCT06250335 | Impact of a Prebiotic Food-enriched Diet ... To learn about the possible effects of a prebiotic food-enriched diet (PreFED) targeting the gut microbiome in participants with ICI-refractory melanoma who are ...

2. reporter.nih.gov reporter.nih.gov/project-details/11167700

Project Details - NIH RePORTER ... prebiotic food enriched dietary intervention influences the gut microbiomeand response to immunotherapy in melanoma. Insights gained may have far-reaching ...

3. mdanderson.org mdanderson.org/cancerwise/nutrivention-food-as-medicine.h00-159776445.html

Nutrivention: Food as medicine The DIET study is a proof-of-concept study that suggests that a high fiber diet can be used to improve immunotherapy outcomes in patients undergoing treatment ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06466434

NCT06466434 | Prebiotic Food-enriched Diet (PreFED) to ... To learn about the possible effects of a prebiotic food-enriched diet (PreFED) targeting the gut microbiome in participants with melanoma who are starting ...

5. cancer.gov cancer.gov/news-events/press-releases/2021/high-fiber-diet-melanoma-immunotherapy

Fiber boosts melanoma patients' response to ... A diet rich in fiber may help some people being treated for melanoma respond to immunotherapy treatment by influencing the gut microbiome.

6. cancer.gov cancer.gov/clinicaltrials/NCI-2024-05150

Prebiotic Food-Enriched Diet to Enhance the Microbiome ... This clinical trial studies the possible effects of a prebiotic food-enriched diet (PreFED) targeting the gut microbiome in patients with stage III-IV ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06747

A Prebiotic Food-Enriched Dietary Intervention Added to ... This phase II trial tests how well adding a prebiotic food enriched diet (PreFED) intervention to standard of care immune checkpoint blockade (ICB) before ...