Combination Radiation and PD-1 Inhibition in Metastatic or Recurrent Renal Cell Carcinoma (RCC)

Study Overview
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Brief Summary
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There are two primary aims in the study: 1) to determine the tolerability and feasibility of combination hypofractionated radiation therapy and PD-1 inhibition with nivolumab, and 2) to determine the ability of hypofractionated radiation therapy to enhance response rate from PD-1 inhibition versus PD-1 inhibition alone by comparing the observed response rate under the combination therapy with a previously reported response rate under inhibition alone.

Detailed Description
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Patients with metastatic or recurrent renal cell cancer who have progressed on standard Tyrosine Kinase Inhibitor (TKI) therapy and who have metastatic or primary tumors suitable for palliative radiation will be eligible for this study. Treatment will consist of nivolumab plus hypofractionated radiation therapy. The primary endpoint will be objective response rate, which will be compared against the historical control of 25% using nivolumab alone as established in the CHECKMATE 025 clinical trial. Patients will continue on nivolumab until disease progression or withdrawal of consent. Follow-up will continue for 2 years.

Official Title
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Combination Radiation and PD-1 Inhibition in Metastatic or Recurrent RCC

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Nivolumab
* Radiation: Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed history of renal cell carcinoma (all variants are acceptable) Progression or recurrence after at least one prior tyrosine kinase inhibitor therapy including, but not limited to: sunitinib, pazopanib, axitinib. At least 1 site (primary or metastasis) amenable to hypofractionated radiation therapy and appropriate for radiation therapy as part of standard of care per medical, urologic or radiation oncologist discretion. NOTE: CT / MRI imaging to have been completed no more than 30 days before enrollment on study. Potential indications for radiation therapy include (but are not limited to): Painful bone or soft tissue metastasis Symptoms from mass effect caused by tumor Prevention of impending symptoms from tumor Hemoptysis due to tumor Limited oligometastasis Isolated region of progression Patients with prior IL-2 treatment are eligible At least 14 days since any prior therapy Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3 Adequate organ and marrow function as defined below: leukocytes ≥ 2,000/mcL absolute neutrophil count ≥ 1,000/mcL platelets ≥ 100,000/mcL total bilirubin within normal institutional limits AST(SGOT) ≤ 2.5 X institutional upper limit of normal ALT(SPGT) ≤ 2.5 X institutional upper limit of normal Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception. Men of child-bearing potential must not donate sperm while on this study and for 90 days after their last study treatment. Exclusion Criteria: Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Men who are trying to father a child. Presence of a condition or abnormality that in the opinion of the study-delegated investigator would compromise the safety of the patient or the quality of the data. Requirement for high dose steroids: dexamethasone > 2 mg per day or equivalent NOTE: Per OPDIVO (Nivolumab) package insert, no formal pharmacokinetic drug-drug interaction studies have been conducted with OPDIVO (Nivolumab) - therefore, no other concomitant medications will exclude potential participants. Life expectancy < 6 months. Other active malignancy (patients with no evidence of disease (NED) or are in remission are eligible). Patient has untreated brain metastases. Patients are eligible after documented stable or improved brain metastases at least 1 month after treatment of brain metastases. History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD-1 Inhibitors used in study. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with active, known or suspected autoimmune disease (not including type 1 diabetes mellitus, hypothyroidism, skin disorders not requiring systemic treatment or conditions not expected to recur). Patients with interstitial lung disease Patients receiving concurrent other cancer-directed therapy including, but not limited to, Tyrosine Kinase Inhibitor (TKI), Mammalian Target Of Rapamycin (mTOR) inhibition and/or chemotherapy.

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 plus radiation<br>Nivolumab plus radiation | Drug: Nivolumab<br>* 240 mg per IV infusion over 60 minutes every 14 days (+/- 2 days) until disease progression or participant withdrawal from study<br>* Other names: OPDIVO;Radiation: Radiation<br>* Radiation to at least 1 site (up to 3) of primary or metastasis, 5 fractions - delivered over 2 weeks, starting 1-3 days post-nivolumab administration. Recommended dose range is 6 Gy-12 Gy per fraction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate (ORR) defined as the sum of partial response (PR) and complete response (CR). Timeframe will be best response from registration to end of treatment. | Every 3 months up to 2 years or progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR at irradiated sites |  | Every 3 months up to 2 years or progression | 
| ORR at un-irradiated sites |  | Every 3 months up to 2 years or progression | 
| Progression free survival (PFS) |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney, renal cell, cancer, metastatic, recurrent