Inulin Gel + Ipilimumab + Nivolumab for Kidney Cancer

Overseen By Cancer AnswerLine

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Michigan Rogel Cancer Center

Must be taking: Ipilimumab, Nivolumab

Must not be taking: Antibiotics, Probiotics, Immunosuppressants, others

Disqualifiers: Autoimmune disease, Brain metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 52 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether a combination of inulin gel, ipilimumab, and nivolumab can safely and effectively treat kidney cancer that has spread or grown nearby. Inulin, a common fiber, may enhance the effectiveness of immune checkpoint inhibitors like ipilimumab and nivolumab. The trial includes two groups: one receiving only the immune drugs, and the other adding inulin gel. It suits individuals with metastatic kidney cancer who have not previously tried these treatments and can tolerate oral therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in 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 be on certain treatments like cytotoxic therapy, biologic agents, or immunosuppressants (except low-dose steroids) shortly before starting the trial. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that the combination of nivolumab and ipilimumab is relatively safe for treating advanced kidney cancer. Patients often tolerate this combo well, though some may experience side effects. Common side effects include fatigue, skin rash, and diarrhea, which are usually manageable.

Early results suggest that the combination of nivolumab, ipilimumab, and inulin gel might be safe and effective. However, as this is a Phase 1/2 trial, researchers are still gathering complete safety information. Inulin, a type of fiber found in many foods, is generally considered safe and often used for gut health.

Overall, while some side effects may occur, existing research indicates that these treatments are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine established immunotherapies with a novel ingredient, inulin gel, which could potentially enhance treatment effectiveness. While standard treatments for kidney cancer, like targeted therapies and checkpoint inhibitors such as nivolumab and ipilimumab, focus on boosting the immune response to cancer cells, adding inulin gel might provide an additional benefit by supporting gut health and possibly modulating the immune system further. This combination could lead to improved patient outcomes by leveraging the synergistic effects of these therapies.

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

Studies have shown that using nivolumab and ipilimumab together effectively treats advanced kidney cancer. In the BIONIKK trial, this combination shrank tumors or halted their growth in 70% of certain patient groups. Real-world data also support its long-term effectiveness, with about 40% of patients experiencing lasting benefits, although some may see early disease progression. In this trial, participants in Arm A will receive nivolumab and ipilimumab. Arm B will explore adding inulin gel, a type of prebiotic fiber, which might enhance these effects by improving gut health and potentially aiding the immune system in fighting cancer. While this combination appears promising, further research is needed to confirm its efficacy. ^{1 2 6 7 8}

Who Is on the Research Team?

Ulka N Vaishampayan

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

The ICON trial is for patients with kidney cell cancer that has spread to other body parts or nearby tissue. Participants should have metastatic or locally advanced renal cell carcinoma and be suitable for treatment with immune checkpoint inhibitors.

Inclusion Criteria

Patient has evaluable or measurable disease as per RECIST 1.1 criteria

Patient meets specified blood count criteria (ANC, platelets, hemoglobin)

I can take medicine by mouth.

Exclusion Criteria

History or current evidence of conditions that might confound study results or interfere with participation

History of hypersensitivity to specified medications or excipients

Known psychiatric or substance abuse disorders that would interfere with trial requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive nivolumab and ipilimumab IV on day 1 of each cycle, with cycles repeating every 21 days for up to 4 cycles. Beginning in cycle 5, patients receive nivolumab monotherapy every 28 days. Patients in Arm B also receive inulin gel PO BID for 52 weeks.

52 weeks

Multiple visits (in-person) for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CT or MRI and blood sample collection.

Up to 3 years

Regular visits (in-person) for monitoring

Open-label extension (optional)

Participants may continue receiving inulin gel PO BID beyond 52 weeks at the discretion of the treating physician and in the absence of disease progression or unacceptable toxicity.

What Are the Treatments Tested in This Trial?

Interventions

• Inulin Gel
• Ipilimumab
• Nivolumab

Trial Overview This trial tests the safety and effectiveness of inulin gel combined with ipilimumab and nivolumab, which are immune system-boosting drugs. The study aims to see if this combination can better attack kidney cancer by improving gut health.

How Is the Trial Designed?

Group I: Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel) Experimental Treatment 8 Interventions

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab monotherapy IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive inulin gel PO BID for 52 weeks in the absence of disease progression or unacceptable toxicity. Patients receiving benefit from study treatment may optionally continue receiving inulin gel PO BID beyond 52 weeks at the discretion of the treating physician and in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the study. Patients may optionally undergo biopsy during screening, on study, and at disease progression.

Group II: Arm A (nivolumab, ipilimumab) Experimental Treatment 7 Interventions

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab monotherapy IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the study. Patients may optionally undergo biopsy during screening, on study, and at disease progression.

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

A 73-year-old hemodialysis patient with metastatic renal cell carcinoma was treated with the combination of ipilimumab and nivolumab, which was administered safely without any adverse events.

This case suggests that ipilimumab-nivolumab can be a viable treatment option for metastatic renal cell carcinoma in patients on hemodialysis, a group that typically has limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. Iwaki, T., Niimi, A., Kano, M., et al.[2022]

In a phase 3 trial involving 1096 patients with untreated advanced renal-cell carcinoma, nivolumab plus ipilimumab significantly improved overall survival rates (75% at 18 months) compared to sunitinib (60% at 18 months), indicating a more effective treatment option for patients with intermediate or poor prognostic risk.

The objective response rate was also higher with nivolumab plus ipilimumab (42%) compared to sunitinib (27%), although both treatments had a high incidence of treatment-related adverse events, with nivolumab plus ipilimumab showing a slightly lower rate of severe (grade 3 or 4) events (46% vs. 63%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. Motzer, RJ., Tannir, NM., McDermott, DF., et al.[2022]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

The PRISM study is investigating whether administering ipilimumab every 12 weeks instead of every 3 weeks, when combined with nivolumab, can reduce severe side effects in patients with metastatic renal cell carcinoma (mRCC) without affecting treatment effectiveness.

This phase II trial aims to recruit 189 participants and will primarily measure the rate of grade 3 or 4 adverse reactions over 12 months, while also assessing progression-free survival and other important health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma. Buckley, HL., Collinson, FJ., Ainsworth, G., et al.[2022]

A patient on hemodialysis with advanced clear-cell renal cell carcinoma successfully received combined immune checkpoint blockade therapy with nivolumab and ipilimumab, showing no significant immune-related adverse events.

This case supports the safety and efficacy of using nivolumab and ipilimumab in patients on hemodialysis, suggesting that renal function does not significantly impact the treatment's pharmacokinetics or safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. Kobayashi, Y., Arai, H., Honda, M.[2023]

A 75-year-old male with metastatic renal cell carcinoma and inferior vena cava tumor thrombus showed significant regression of the tumor and pulmonary nodules after treatment with nivolumab and ipilimumab, indicating potential efficacy of this combination therapy.

Post-surgical histopathological analysis revealed no viable malignant cells, suggesting that nivolumab plus ipilimumab may effectively treat advanced cases of renal cell carcinoma, even in complex scenarios involving tumor thrombus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete response of metastatic renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus ipilimumab. Hayashida, M., Miura, Y., Noda, T., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39705641/

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients ...

2. ascopubs.org ascopubs.org/doi/10.1200/CCI.24.00132

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients with I/P-risk mRCC.

3. nature.com nature.com/articles/s41698-025-00912-x

Enhanced efficacy of ipilimumab plus nivolumab in ... The BIONIKK trial revealed that ipilimumab plus nivolumab (Ipi/Nivo) achieved a 70% objective response rate in angiogenic cluster1/2 versus 41% in cluster4/5.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01516-3/fulltext

Nivolumab plus ipilimumab versus sunitinib for first-line ... Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143925002601

Comparison of real-world outcomes between nivolumab ... Comparison of real-world outcomes between nivolumab plus ipilimumab and lenvatinib plus pembrolizumab or nivolumab plus cabozantinib combination ...

6. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-kidney-cancer/160902-asco-2025-nivolumab-plus-ipilimumab-vs-sunitinib-for-first-line-treatment-of-advanced-renal-cell-carcinoma-final-analysis-from-the-phase-3-checkmate-214-trial.html

ASCO 2025: Nivolumab plus Ipilimumab vs Sunitinib for ... The hazard ratio for overall survival remained stable and in favor of NIVO + IPI versus sunitinib over > 9 years of median follow-up in the ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1712126

Nivolumab plus Ipilimumab versus Sunitinib in Advanced ... Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study.

8. jitc.bmj.com jitc.bmj.com/content/13/2/e010958

Efficacy and safety of nivolumab plus ipilimumab in ... Similarly, the median PFS was 4.3 months (95% CI: 1.4 – NE) for nephrectomy patients and 5.1 months (95% CI: 2.3 to 9.6) for those without ...