Stereotactic Ablative Radiation Therapy for Metastatic Unresected Renal Cell Carcinoma Receiving Immunotherapy

What is the Purpose of this Study?

This study focuses on people who have renal cell cancer that has spread beyond the kidney and for whom surgery is not currently recommended (or who have chosen not to have surgery). The study aims to determine whether the addition of radiation therapy to the usual immune therapy can increase the time that the patient’s renal cancer does not get worse. The usual approach for patients with metastatic renal cell cancer who are not having surgery is treatment with immune therapy alone or immune therapy plus a targeted therapy drug called a VEGF inhibitor. The addition of radiation therapy to the usual treatment may stabilize the patient’s cancer or possibly cause it to shrink, but it could also cause side effects. Researchers will evaluate whether the study approach increases the time without cancer progressing by 6 months or more compared to the usual approach. The study has 2 groups, and patients are randomly assigned to 1 of the 2 groups. Group 1 will receive the usual immune therapy as an infusion through a vein in the arm, and if they also receive a VEGF drug, they will receive this as a pill taken orally. Group 2 will receive radiation therapy plus the usual immune therapy.

Eligibility

* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
* History/physical examination within 45 days prior to registration

Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
* History/physical examination within 45 days prior to registration
* CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
* Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\>= 3 factors)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
* Patient not recommended for or refused immediate cytoreductive nephrectomy
* Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
* Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
* Age \>= 18
* Karnofsky performance status \>= 60 within 45 days prior to registration
* Hemoglobin \>= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
* Platelet count \>= 50,000/mm\^3 (within 45 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 45 days prior to registration)
* Calculated (Calc.) creatinine clearance \>= 30 mL/min (within 45 days prior to registration)
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault Equation
* For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (within 45 days prior to registration)
* Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\< 3 x upper limit of normal (ULN) or \< 5 x ULN if hepatic metastases present (within 45 days prior to registration)
* Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
* The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
* Patients with untreated or unstable brain metastases or cranial epidural disease
* Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
* Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated \> 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Severe, active comorbidity defined as follows:
* Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
* Active tuberculosis (purified protein derivative \[PPD\] response without active tuberculosis \[TB\] is allowed)
* Uncontrolled hypertension (systolic blood pressure \[BP\] \>= 190 mmHg or diastolic BP \> 110 mmHg)
* Major surgery requiring hospital admission =\< 28 days prior to registration
* Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
* Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-ST elevation myocardial infarction \[NSTEMI\], cerebrovascular accident \[CVA\], etc) events within 180 days prior to registration
* Active New York (NY) Heart Association class 3-4 heart failure symptoms
* Moderate or severe hepatic impairment (Child-Pugh B or C)
* Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis \> 30 days prior to registration is allowed)
* Unstable cardiac arrhythmia within 180 days prior to registration
* History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
* History of or active inflammatory bowel disease
* Malabsorption syndrome within 45 days prior to registration
* Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =\< 45 days prior to registration

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Where can I participate?

CS Cancer at Beverly Hills : Maria Tarallo
CS Cancer at Cedars-Sinai Medical Center : Maria Tarallo

More about this Clinical Trial

What is the full name of this clinical trial?

NRG-GU012: Randomized Phase II Stereotactic Ablative Radiation Therapy For Metastatic Unresected Renal Cell Carcinoma Receiving Immunotherapy

Study Details

Disease Type/Condition

Kidney

Principal Investigator

Ballas, Leslie

Co-Investigators

Andrew Horodner, Andrew Schumacher, Anthony Nguyen, David Chan, David Hoffman, Edwin Posadas, Hugo Hool, Jeremy Lorber, Jun Gong, Justin Wayne Tiulim, Kevin Scher, Rebecca Philipson, Samuel Zhang, Swati Sikaria, Syed Jilani, Thomas Lowe, Thyra Endicott, Usama Mahmood, Vanessa Dickey

Age Group

Adult

Phase

IRB Number

STUDY00004942

ClinicalTrials.gov ID

NCT05327686

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Maria Tarallo

Email

Maria.Tarallo@cshs.org