Nivolumab + Ipilimumab With Immunostimulatory Embolization for Stage 4 Renal Cell Carcinoma With Unresected Primary

Study Overview
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Brief Summary
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This single center phase 1 trial will study the combination of nivolumab+ipilimumab with embolization in participants with renal cell carcinoma. The study will evaluate the safety of embolotherapy in patients with metastatic RCC receiving nivolumab+ipilimumab. The hypothesis is that the number of serious adverse events will be no greater than the number of serious adverse events for both therapies combined.

Detailed Description
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Previously untreated subjects with stage 4 RCC and unresected primary tumor or metastasis amenable to embolization will undergo two cycles of combination immune checkpoint inhibition (ICI) therapy, embolization of the target tumor, then resume ICI therapy. Study ends with safety and efficacy assessment at 6 months. Correlative blood and tissue specimens will be obtained.

Official Title
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UPCC06820 Phase 1 Trial of Nivolumab + Ipilimumab With Immunostimulatory Embolization for Stage 4 Renal Cell Carcinoma With Unresected Primary

Conditions
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Renal Cell Carcinoma, Renal Cell Carcinoma Stage IV

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Ipilimumab
* Device: bland embolization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic renal cell carcinoma with unresected primary tumor or with metastasis amenable to embolization. No prior immune checkpoint therapy Primary tumor or metastasis amenable to percutaneous embolization per review by the treating interventional oncologist · Patent feeding artery to tumor > 2 mm diameter without macroscopic arteriovenous fistula/shunt Additional metastatic site > 1 cm assessable for response by RECIST 1.1 Adequate organ function by screening laboratory studies within 30 days of embolization platelets > 50K, correctable by transfusion INR < 1.5, correctable by transfusion creatinine < 2.0 ECOG performance status 0-2 Age ≥ 18 years Have signed the current approved informed consent form and be willing and able to comply with this protocol Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study drug Women of childbearing potential must have a negative serum or urine pregnancy test Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose Exclusion Criteria: Untreated CNS metastasis Autoimmune disorder; subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment Immunodeficiency syndrome Glucocorticoid (> 10 mg daily prednisone equivalents) or immunosuppressant therapy Active infection requiring systemic therapy Any other medical or personal condition that, in the opinion of the site investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical trial. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection Contrast allergy not mitigated by usual prophylaxis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipilimumab +Nivolumab with Embolization<br>Patients initiate ICI therapy with Nivolumab 3 mg/kg + ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, followed by nivolumab 480mg flat dose IV every four weeks for a total of 6 months of therapy unless stopped for confirmed progression or intolerable toxicities. Patients will receive 2 cycles of systemic therapy followed by embolization of their primary tumor or metastatic lesion(s) and continue systemic therapy subsequently. | Drug: Nivolumab<br>* Nivolumab 3 mg/kg IV every four weeks, first in combination with capecitabine then alone<br>* Other names: Opdivo;Drug: Ipilimumab<br>* ipilimumab 1/mg/kg IV every 3 weeks x 4 cycles, in combination with Nivolumab<br>* Other names: Yervoy;Device: bland embolization<br>* Lipiodol:ethanol embolization of their primary or target tumor<br>* Other names: trans-arterial embolization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of serious adverse events | SAE rate following embolization in patients | Serious adverse events will be recorded from time of informed to consent to 100 days after the end of study intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Objective response rate by RECIST 1.1 | Measured from baseline to 6 months post initiation | 
| Characterization of immune cells | Characterization of tumor-infiltrating leukocytes in primary and metastatic lesions before and after embolotherapy | From baseline to 12 weeks post initiation of therapy | 
| PD-L1 | Percentage of PD-L1 stain positivity in the primary tumor biopsy of participants | From baseline to 12 weeks post initiation of therapy |