Inulin Gel in Combination With Ipilimumab and Nivolumab for the Treatment of Metastatic or Locally Advanced Kidney Cell Cancer, ICON Trial

Phase 1

Not yet recruiting

• Conditions: Locally Advanced Clear Cell Renal Cell Carcinoma; Locally Advanced Sarcomatoid Renal Cell Carcinoma; Metastatic Sarcomatoid Renal Cell Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8
• Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Ipilimumab; Dietary Supplement: Inulin; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Other: Questionnaire Administration

• Registration Number: NCT06866262
• Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-04
• Study First Submitted QC: 2025-03-04
• Study First Posted: 2025-03-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-01
• Last Update Posted: 2025-05-02
• Study Start: 2025-06-01
• Primary Completion: 2031-06-01
• Study Completion: 2031-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

• Patient is ≥ 18 years of age on the day of signing informed consent.

• Candidate for ipilimumab and nivolumab therapy for metastatic renal cancer per the treating physician investigator.

• Patient has a performance status of ≤ 2 on the Zubrod performance scale.

• Patient has a histological or cytological diagnosis of renal cancer with clear cell or sarcomatoid component.

• Radiologic or clinical evidence of metastatic disease, or progressive locally advanced disease.

• Absolute neutrophil count ≥ 1,500/uL.

• Platelets ≥ 75K/μL.

• Hemoglobin ≥ 8.5 g/dL.

• Calculated creatinine clearance is ≥ 30 ml/min as per the Cockroft-Gault formula.

• Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) OR total bilirubin levels ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN.

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN except for patients with liver metastases, AST/ALT should be ≤ 5 x ULN.

• Patient received no prior therapy for metastatic disease. Adjuvant therapy is permitted if completed at least 6 months prior to study therapy start.

• Patient has evaluable or measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Bone metastases, pleural effusion or ascites will be considered evaluable disease sites.

  • Tumor mass: Must be accurately measurable in at least 1 dimension (longest diameter to be recorded) with a minimum size of:

    • 10 mm by CT scan (CT scan slice thickness no greater than 5 mm,

Or:

• 20 mm by chest X-ray (if clearly defined and surrounded by aerated lung). With or without malignant lymph nodes: ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness must be ≤ 5 mm). The measurement should be two dimensions at axial plane. The short axis should be in perpendicular to long diameter.

  • Ability to understand and the willingness to review and sign a written informed consent.
  • Both male and female patients must agree to use adequate contraceptive measures to prevent pregnancy throughout the duration of study therapy and a minimum of -5 months after stopping therapy per package insert of ipilimumab and nivolumab.
  • Ability to ingest oral therapy.
  • Female patient of childbearing capacity has a negative pregnancy test within 7 days of starting study therapy.

Exclusion Criteria

• The subject has received cytotoxic therapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) or immunosuppressants (excluding steroids) within 4 weeks or antibiotics within 2 weeks of starting study therapy.
• Patient is currently enrolled in another clinical trial testing another investigational agent, or concurrently in another approved systemic anti-cancer therapy for renal cancer.
• Patient is on chronic systemic steroid therapy at doses > 10 mg/day prednisone equivalent or on any other immunosuppressive therapy within 7 days prior to day 1 of therapy. Exception-Replacement steroid doses for adrenal insufficiency are permitted as necessary.
• Subjects with active and uncontrolled autoimmune disease. Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.
• Patient has active brain metastases or leptomeningeal metastases. Patients are eligible if brain metastases are adequately treated, and patients are neurologically stable (except for residual signs or symptoms related to the cancer or central nervous system treatment).
• Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or make study participation not in the best interest of the patient, in the opinion of the treating investigator.
• Patient has known psychiatric or substance abuse disorders that, in the opinion of the investigator, would interfere with cooperation with the requirements of the trial.
• Pregnant patients or patients planning donation of sperm or breast milk during the therapy and for a minimum of 5 months after stopping therapy.
• Lactating patients if they do not agree to discontinue breast feeding through the entire duration of study participation and for 5 months after stopping therapy.
• History of another metastatic/relapsed active malignancy. Localized skin cancers such as basal cell or squamous cell cancer are allowed.
• Intractable nausea and vomiting refractory to therapy with antiemetics.
• History of hypersensitivity to ipilimumab, nivolumab, inulin or the formulations excipients.
• Known diagnosis of malabsorption disorder.
• Concurrent use of probiotics or antibiotics.
• Patients with a history of colectomy and/or gastric bypass.
• Patients with a known diagnosis of active inflammatory bowel disease or irritable bowel syndrome.
• History of organ transplant or stem cell/bone marrow transplant.
• Patients with active Clostridium difficile infection within 3 months before therapy start. Active infection is defined as a stool sample positive for Clostridium difficile toxin by enzyme immunoassay (EIA) and either symptoms (frequent loose stools) OR imaging findings consistent with toxic megacolon.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (nivolumab, ipilimumab)	Biopsy	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.
Arm A (nivolumab, ipilimumab)	Biospecimen Collection	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.
Arm A (nivolumab, ipilimumab)	Computed Tomography	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.
Arm A (nivolumab, ipilimumab)	Ipilimumab	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.
Arm A (nivolumab, ipilimumab)	Magnetic Resonance Imaging	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.
Arm A (nivolumab, ipilimumab)	Nivolumab	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.
Arm A (nivolumab, ipilimumab)	Questionnaire Administration	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Biopsy	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Biospecimen Collection	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Computed Tomography	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Inulin	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Ipilimumab	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Magnetic Resonance Imaging	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Nivolumab	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.
Safety run-in & Arm B (nivolumab, ipilimumab, inulin gel)	Questionnaire Administration	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.

Primary Outcome Measures

Name	Time	Method
6-month progression free survival (PFS)	At 6 months	Will give an estimate and 95% confidence interval for the difference in the 6-month PFS rate between the combination arm and the single agent arm. This will be determined using binomial statistics. To allow for possible variability in the timing of the 6-month progression assessment, the 6-month PFS rate will be defined as the Kaplan-Meier estimate at 200 days after treatment initiation.
Incidence of inulin gel related adverse events	Up to 30 days after the last dose of inulin gel	Will be reported descriptively. Toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Secondary Outcome Measures

Name	Time	Method
Overall response rate	From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years	Will be assessed per Response Evaluation Criteria in Solid Tumors 1.1 criteria. An exact test for binomial proportion will be used. Will be assessed descriptively. Will be estimated with 95% confidence interval. Binomial statistics will be used for the binary outcomes.
Incidence of adverse events	Up to 30 days after the last dose of treatment	Toxicity will be assessed according to the CTCAE, version 5.0.
PFS	From treatment start date to date of first documented disease relapse/progression, or death from cancer whichever occurs first, assessed up to 3 years	Will be assessed descriptively. Will be estimated with 95% confidence intervals, for each treatment group separately. Kaplan-Meier plots for the time-to-event outcomes.
Overall survival	From treatment start date to death or last follow up, assessed up to 3 years	Will be assessed descriptively. Will be estimated with 95% confidence intervals, for each treatment group separately. Kaplan-Meier plots for the time-to-event outcomes.

Trial Locations

Locations (1)

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States