A Randomized Trial of Maintenance Systemic Therapy After Radiation for Oligometastatic Renal Cell Carcinoma (ASTROs)

Eligibility Criteria

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