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

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 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.

What data supports the effectiveness of the drug combination of Inulin Gel, Ipilimumab, and Nivolumab for kidney cancer?

Research shows that the combination of nivolumab and ipilimumab is effective as a first-line treatment for advanced kidney cancer, producing positive responses in patients. This combination is considered a new standard of care for patients with certain types of advanced kidney cancer. ^{1 2 3 4 5}

Is the combination of Inulin Gel, Ipilimumab, and Nivolumab safe for humans?

The combination of Ipilimumab and Nivolumab has been studied for kidney cancer and shows manageable safety, though it can cause significant side effects in some patients. These side effects are often related to the immune system and can be serious, but they are generally considered manageable with proper medical care. ^{3 6 7 8 9}

How is the treatment with Inulin Gel, Ipilimumab, and Nivolumab different for kidney cancer?

This treatment is unique because it combines Inulin Gel with the immune checkpoint inhibitors Ipilimumab and Nivolumab, which are already used for advanced kidney cancer. The addition of Inulin Gel, which is not typically part of standard kidney cancer treatments, may offer a novel approach, although its specific role and benefits in this combination are not detailed in the available research. ^{1 2 3 9 10}

What is the purpose of this trial?

This phase I/II trial tests the safety and effectiveness of inulin gel in combination with ipilimumab and nivolumab in treating patients with kidney cell cancer (renal cell carcinoma \[RCC\]) that has spread from where it first started (primary site) to other places in the body (metastatic) or has spread to nearby tissue or lymph nodes (locally advanced). Inulin is a common food additive fermentable prebiotic fiber beneficial for a healthy gut microbiome. The microbiome is the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on and inside the body. Inulin may also be used for cancer prevention and heart health, but there is less evidence to support those uses. The gut microbiome profile may improve the effectiveness of drugs called immune checkpoint inhibitors, such as ipilimumab and nivolumab. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving inulin gel in combination with ipilimumab and nivolumab may be safe and effective in treating in patients with metastatic or locally advanced RCC.

Research Team

Ulka N Vaishampayan

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Tailored immunotherapy approach with nivolumab with or without nivolumab plus ipilimumab as immunotherapeutic boost in patients with metastatic renal cell carcinoma (TITAN-RCC): a multicentre, single-arm, phase 2 trial. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. [2022]

3. England 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. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Complete response of metastatic renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus ipilimumab. [2022]

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

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. [2022]

6. England 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. [2022]

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

Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study. [2022]

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

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]

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

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]

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

Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM). [2023]