Investigator-Initiated Trial of Combined Ipilimumab, Nivolumab and Stereotactic Radiation in Patients With Metastatic Clear-Cell RCC (ccRCC) Who Have Failed Treatment With Single-Agent Nivolumab

Study Overview
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Brief Summary
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The purpose of this study is to see if continued nivolumab with the addition of ipilimumab plus hypo-fractionated stereotactic radiation (sTR) of a single lesions results in partial or complete responses in patients with metastatic ccRCC who fail initial treatment with single agent nivolumab.

Official Title
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An Investigator-Initiated Trial of Combined Ipilimumab, Nivolumab and Stereotactic Radiation in Patients With Metastatic Clear-Cell RCC (ccRCC) Who Have Failed Treatment With Single-Agent Nivolumab

Conditions
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Clear Cell Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Ipilimumab
* Radiation: Steriotactic radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of metastatic ccRCC. Age 18 years and older ECOG 0-1 Progressive disease after treatment with single-agent nivolumab Life expectancy at least 3 months Presence of measurable disease per RECIST 1.1 criteria Presence of a metastatic lesion greater than 1 cm in size that is amenable to radiation treatment Adequate organ system function WOCBP and men who are sexually active with WOCBP must agree to use appropriate method(s) of contraception. Exclusion Criteria: Patients are excluded if they have active brain metastases or leptomeningeal metastases (exceptions outlined in the protocol). Active, known or suspected autoimmune disease, such as systemic lupus erythematosus, that require treatment with immune suppressing drugs. Note: 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, or conditions not expected to recur in the absence of an external trigger Presence of a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of study drug administration. Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Unstable angina or uncontrolled congestive heart failure Uncontrolled hypercalcemia Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Presence of other malignant diseases, except non-melanoma skin care History of allergy to study drug components. History of severe hypersensitivity reaction to any monoclonal antibody. Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days of registration. Women must not be pregnant or breastfeeding. WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to registration. Any other medical condition for which treatment with ipilimumab or nivolumab would be medically contraindicated

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: Nivolumab + Ipilimumab + SRT<br> | Drug: Nivolumab<br>* Nivolumab will be given every 21 days for the first 12 weeks at a dose of 3mg/kg. After 12 weeks, the dose will be 240mg and will be given every 14 days.<br>* Other names: opdivo;Drug: Ipilimumab<br>* Ipilimumab will be given at a dose of 1mg/kg every 21 days for up to 12 weeks.<br>Radiation: Steriotactic radiation therapy<br>* The dose of radiation will be 6 Gy daily x 5 days. Radiation will be given between the first and second doses of ipilimumab plus nivolumab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with a partial or complete response | The response rate of combined ipilimumab and nivolumab plus STR will be determined using irRECIST criteria. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS will be determined from the onset of treatment to the time of documented disease progression. | 2 years |