Clinical trial Recruiting at 303 sites Phase 2 Interventional Ages 18 and up

Combining Stereotactic Radiation with Immune Therapy for Advanced Kidney Cancer

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

Run by NRG Oncology · NCT05327686 · Data updated 2026-11-12

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.

More Metastatic Renal Cell Carcinoma trials

Quick facts

PhasePhase 2
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment240 (estimated)
SponsorNRG Oncology
Academic / other
Drugs / interventionschemotherapy, radiation, prednisone, nivolumab, ipilimumab, avelumab, pembrolizumab, Axitinib, cabozantinib, lenvatinib, immunotherapy
Locations348 sites (Birmingham, Alabama and 347 other locations)
StatusRecruiting
StartedFebruary 1, 2023
Main results expectedJune 15, 2028
Study endsJune 15, 2033
Registry record updatedOctober 23, 2026
Trial IDNCT05327686 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

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

Probably 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.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

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

Who can join: the full rules

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 it's running

  • Mayo Clinic Hospital in Arizona
    Phoenix, Arizona, United States
    Recruiting
  • Highlands Oncology Group - Fayetteville
    Fayetteville, Arkansas, United States
    Recruiting
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas, United States
    Recruiting
  • Highlands Oncology Group - Rogers
    Rogers, Arkansas, United States
    Recruiting
  • Highlands Oncology Group
    Springdale, Arkansas, United States
    Recruiting
  • Tower Cancer Research Foundation
    Beverly Hills, California, United States
    Recruiting
Show 44 more locations
  • Mills-Peninsula Medical Center
    Burlingame, California, United States
    Recruiting
  • UC San Diego Health System - Encinitas
    Encinitas, California, United States
    Recruiting
  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
    Irvine, California, United States
    Recruiting
  • UC San Diego Moores Cancer Center
    La Jolla, California, United States
    Recruiting
  • The Angeles Clinic and Research Institute - West Los Angeles Office
    Los Angeles, California, United States
    Recruiting
  • Los Angeles General Medical Center
    Los Angeles, California, United States
    Recruiting
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, United States
    Recruiting
  • Cedars-Sinai Medical Center
    Los Angeles, California, United States
    Recruiting
  • Memorial Medical Center
    Modesto, California, United States
    Recruiting
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, United States
    Recruiting
  • Sutter Roseville Medical Center
    Roseville, California, United States
    Recruiting
  • Sutter Medical Center Sacramento
    Sacramento, California, United States
    Recruiting
  • UC San Diego Medical Center - Hillcrest
    San Diego, California, United States
    Recruiting
  • UCSF Medical Center-Mission Bay
    San Francisco, California, United States
    Recruiting
  • Mills Health Center
    San Mateo, California, United States
    Recruiting
  • Ridley-Tree Cancer Center
    Santa Barbara, California, United States
    Recruiting
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, United States
    Recruiting
  • UCHealth University of Colorado Hospital
    Aurora, Colorado, United States
    Recruiting
  • UCHealth - Cherry Creek
    Denver, Colorado, United States
    Recruiting
  • Poudre Valley Hospital
    Fort Collins, Colorado, United States
    Recruiting
  • Cancer Care and Hematology-Fort Collins
    Fort Collins, Colorado, United States
    Recruiting
  • UCHealth Greeley Hospital
    Greeley, Colorado, United States
    Recruiting
  • UCHealth Highlands Ranch Hospital
    Highlands Ranch, Colorado, United States
    Recruiting
  • UCHealth Lone Tree Health Center
    Lone Tree, Colorado, United States
    Recruiting
  • Medical Center of the Rockies
    Loveland, Colorado, United States
    Recruiting
  • Beebe Medical Center
    Lewes, Delaware, United States
    Recruiting
  • Beebe South Coastal Health Campus
    Millville, Delaware, United States
    Recruiting
  • Helen F Graham Cancer Center
    Newark, Delaware, United States
    Recruiting
  • Medical Oncology Hematology Consultants PA
    Newark, Delaware, United States
    Recruiting
  • Christiana Care Health System-Christiana Hospital
    Newark, Delaware, United States
    Recruiting
  • Beebe Health Campus
    Rehoboth Beach, Delaware, United States
    Recruiting
  • Christiana Care Health System-Wilmington Hospital
    Wilmington, Delaware, United States
    Recruiting
  • Mount Sinai Comprehensive Cancer Center at Aventura
    Aventura, Florida, United States
    Recruiting
  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    Hollywood, Florida, United States
    Recruiting
  • Mayo Clinic in Florida
    Jacksonville, Florida, United States
    Recruiting
  • Moffitt Cancer Center at Speros
    Land O' Lakes, Florida, United States
    Recruiting
  • Miami Cancer Institute
    Miami, Florida, United States
    Recruiting
  • Mount Sinai Medical Center
    Miami Beach, Florida, United States
    Recruiting
  • Memorial Hospital West
    Pembroke Pines, Florida, United States
    Recruiting
  • Moffitt Cancer Center at SouthShore
    Ruskin, Florida, United States
    Recruiting
  • Moffitt Cancer Center-International Plaza
    Tampa, Florida, United States
    Recruiting
  • Moffitt Cancer Center - McKinley Campus
    Tampa, Florida, United States
    Recruiting
  • Moffitt Cancer Center
    Tampa, Florida, United States
    Recruiting

+298 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: William A Hall — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 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.