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

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 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.

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.
• Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease must not require immediate CNS specific treatment at the time of study registration. Patients who have completed CNS therapy prior to starting therapy and clinically stabilized are also eligible.
• 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.