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Combining Stereotactic Radiation with Immune Therapy for Advanced Kidney Cancer

Randomized Phase II Stereotactic Ablative Radiation Therapy (SABR) for Metastatic Unresected Renal Cell Carcinoma (RCC) Receiving Immunotherapy (SAMURAI)

Phase 2 Interventional NRG Oncology · NCT05327686

This study is testing whether adding a special type of radiation therapy to standard immune treatment can help people with advanced kidney cancer live longer and feel better.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment240 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology Academic / other
Drugs / interventionschemotherapy, radiation, prednisone, nivolumab, ipilimumab, avelumab, pembrolizumab, Axitinib, cabozantinib, lenvatinib, immunotherapy
Locations318 sites (Birmingham, Alabama and 317 other locations)
Trial IDNCT05327686 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of adding stereotactic ablative radiation therapy (SABR) to standard immunotherapy in patients with unresectable or metastatic renal cell carcinoma. The study aims to determine if this combination improves outcomes such as progression-free survival compared to immunotherapy alone. Participants will receive high-precision radiation targeting the primary tumor alongside immune-boosting treatments like monoclonal antibodies. The trial will also assess safety, toxicity, and overall survival rates among the different treatment arms.

Who should consider this trial

Good fit: Ideal candidates include individuals with pathologically confirmed metastatic or unresectable renal cell carcinoma who are not recommended for immediate surgery.

Not a fit: Patients with early-stage renal cell carcinoma or those who are candidates for immediate cytoreductive nephrectomy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with advanced renal cell carcinoma.

How similar studies have performed: Other studies have shown promise in combining radiation with immunotherapy, suggesting potential for success in this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Birmingham, Alabama and 317 other locations

+268 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Renal Cell CarcinomaStage III Renal Cell Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8Unresectable Renal Cell Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.