∙ In order to be eligible for trial participation, patients must have:

• The participant provides written informed consent for the trial.

• Pathologically confirmed diagnosis of RCC with a clear cell component.

• Be willing and able to undergo biopsy of a lesion planned for definitive RT. If a lesion amenable to SBRT was biopsied prior to enrollment, this material can be used in lieu of a planned biopsy if the tissue is available for review at MD Anderson.

‣ Patients may be allowed on this trial without a biopsy if they are deemed medically unfit for biopsy or if the biopsy poses undue risk in the opinion of the treating physician(s).

• Be ≥18 years of age on the day of signing informed consent.

• ECOG performance status 0-1.

∙ NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is ambulatory for the purpose of assessing their performance status.

• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

• Oligometastatic RCC patients (≤5 metastatic lesions at the time of study entry). Per the discretion of the treating clinicians, we will not count lung lesions \<1 cm short axis and LNs \<1.5 cm short axis as these lesions are often equivocal.

‣ CNS disease will be allowed and the number of CNS lesions counted towards the number of metastatic lesions for the purposes of study entry.

• Demonstrate adequate organ function as defined in the table below, all screening labs should be performed within 10 days prior to enrollment.

• At least one site, which in the opinion of the treating radiation oncologist, is treatable with definitive RT and can be biopsied.

• Criteria for known Hepatitis B and C positive subjects. Hepatitis B and C screening tests are not required unless:

• •Known history of HBV or HCV infection

⁃ As mandated by local health authority

• Hepatitis B positive subjects • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.

• • Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.

• Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.

• • Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.

• Table Adequate Organ Function Laboratory Values System Laboratory Value --Hematological --Absolute neutrophil count (ANC) ≥1500/µL --Platelets ≥100 000/µL --Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La --Renal --Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN Hepatic --Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN --AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)

⁃ -Coagulation International normalized ratio (INR) OR prothrombin time (PT)

⁃ -Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

⁃ -ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);

• \-- AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); ----GFR=glomerular filtration rate; ULN=upper limit of normal.

• a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.

• b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.