Overview

To learn if adding 1 year of therapy with pembrolizumab can help to continue to control RCC after radiation therapy.

Eligibility

Inclusion Criteria:

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

1. The participant provides written informed consent for the trial.
2. Pathologically confirmed diagnosis of RCC with a clear cell component.
3. 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.
   1. 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).
4. Be ≥18 years of age on the day of signing informed consent.
5. 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.
          1. 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.
          2. 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.
               1. CNS disease will be allowed and the number of CNS lesions counted towards the
                  number of metastatic lesions for the purposes of study entry.
          3. Demonstrate adequate organ function as defined in the table below, all screening labs
             should be performed within 10 days prior to enrollment.
          4. At least one site, which in the opinion of the treating radiation oncologist, is
             treatable with definitive RT and can be biopsied.
          5. 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
          6. 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.
          7. 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.
             Exclusion Criteria:
             The patient must be excluded from participating in the trial based on the following
             conditions:
        1. The patient must have received their last dose of systemic therapy ≥24 weeks prior to
        initiation of their first dose of RT if this therapy included immunotherapy (e.g.
        pembrolizumab, nivolumab, ipilimumab, etc.) or ≥4 weeks prior to initiation of the first
        dose of radiation if this systemic therapy did not include immunotherapy.
        2. Immunocompromising conditions, as follows:
          -  Known acute or chronic human immunodeficiency virus (HIV) infection
          -  History of primary immunodeficiency
          -  History of allogeneic tissue/solid organ transplant
          -  Current or prior use of immunosuppressive medication within 7 days before the first
             dose of study treatment, except for topical, ocular, intranasal, and inhaled
             corticosteroids, or systemic corticosteroids at an equivalent dose ≤10 mg of
             prednisone daily.
             3. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial as determined by the treating physician
             and/or member of the study team.
             4. Patients with a prior history of grade 3 or worse immune-related adverse events
             attributed to checkpoint inhibitors (PD-1, PD-L1, or CTLA-4), except endocrine adverse
             events with appropriate hormone replacement.
             5. Has received a live vaccine or live-attenuated vaccine within 30 days before the
             first dose of study intervention. Administration of killed vaccines is allowed.
             6. Per the opinion of the treating physician of study team has cognitive impairments
             such that appropriate informed consent cannot be obtained or that he/she cannot
             participate in required study activities.
               1. Diffuse metastatic processes including leptomeningeal disease, diffuse bone
                  marrow involvement, and peritoneal carcinomatous, which by the discretion of the
                  treating physician cannot be treated definitively.
               2. Is pregnant, breast feeding, or expecting to conceive within the projected
                  duration of the trial at the screening visit and at least one of the following
                  conditions apply.
          -  Not a woman of childbearing potential (WOCBP) as defined in Appendix OR
          -  A WOCBP who agrees to follow the contraceptive guidance in Appendix during the
             treatment period and for at least 120 days (corresponding to time needed to eliminate
             any study treatment(s) (pembrolizumab and/or any active comparator/combination) plus
             30 days (a menstruation cycle) after the last dose of study treatment.
             3. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
             enrollment. If the urine test is positive or cannot be confirmed as negative, a serum
             pregnancy test will be required.