Phase I/II Trial of Inulin Gel in Combination With Ipilimumab and Nivolumab in Advanced Renal Cell Carcinoma [ICON 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.
• 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 systemic anti-cancer therapy for metastatic disease.
• 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.