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Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial

RecruitingPhase 2

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

Who can join

Ages 18 and older · All sexes

Full eligibility 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

About the study

This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.

What is being tested

Sponsor: NRG Oncology · Participants: 240 · Started: Feb 1, 2023

Contact the study team

Official record on ClinicalTrials.gov — NCT05327686

Locations in the U.S.

ArizonaKingman Regional Medical Center, Kingman
Mayo Clinic Hospital in Arizona, Phoenix
ArkansasUniversity of Arkansas for Medical Sciences, Little Rock
CaliforniaPCR Oncology, Arroyo Grande
Tower Cancer Research Foundation, Beverly Hills
Mills-Peninsula Medical Center, Burlingame
UC San Diego Health System - Encinitas, Encinitas
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care, Irvine
UC San Diego Moores Cancer Center, La Jolla
Cedars-Sinai Medical Center, Los Angeles
Los Angeles General Medical Center, Los Angeles
USC / Norris Comprehensive Cancer Center, Los Angeles
Memorial Medical Center, Modesto
UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange
Sutter Cancer Centers Radiation Oncology Services-Roseville, Roseville
Sutter Roseville Medical Center, Roseville
Sutter Medical Center Sacramento, Sacramento
UC San Diego Medical Center - Hillcrest, San Diego
UCSF Medical Center-Mission Bay, San Francisco
Mills Health Center, San Mateo
Ridley-Tree Cancer Center, Santa Barbara
Sutter Pacific Medical Foundation, Santa Rosa
ColoradoUCHealth University of Colorado Hospital, Aurora
UCHealth - Cherry Creek, Denver
Cancer Care and Hematology-Fort Collins, Fort Collins
Poudre Valley Hospital, Fort Collins
UCHealth Greeley Hospital, Greeley
UCHealth Highlands Ranch Hospital, Highlands Ranch
UCHealth Lone Tree Health Center, Lone Tree
Medical Center of the Rockies, Loveland
DelawareBeebe Medical Center, Lewes
Beebe South Coastal Health Campus, Millville
Christiana Care Health System-Christiana Hospital, Newark
Helen F Graham Cancer Center, Newark
Medical Oncology Hematology Consultants PA, Newark
Beebe Health Campus, Rehoboth Beach
Christiana Care Health System-Wilmington Hospital, Wilmington
FloridaMount Sinai Comprehensive Cancer Center at Aventura, Aventura
Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood
Mayo Clinic in Florida, Jacksonville
Miami Cancer Institute, Miami
Mount Sinai Medical Center, Miami Beach
Memorial Hospital West, Pembroke Pines
IdahoSaint Alphonsus Cancer Care Center-Boise, Boise
Saint Alphonsus Cancer Care Center-Caldwell, Caldwell
Saint Alphonsus Cancer Care Center-Nampa, Nampa
IllinoisCentralia Oncology Clinic, Centralia
Northwestern University, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
Carle at The Riverfront, Danville
Northwestern Medicine Cancer Center Kishwaukee, DeKalb
Cancer Care Specialists of Illinois - Decatur, Decatur
Decatur Memorial Hospital, Decatur
Carle Physician Group-Effingham, Effingham
Crossroads Cancer Center, Effingham
Northwestern Medicine Cancer Center Delnor, Geneva
Northwestern Medicine Glenview Outpatient Center, Glenview
Northwestern Medicine Grayslake Outpatient Center, Grayslake
Ingalls Memorial Hospital, Harvey
Northwestern Medicine Lake Forest Hospital, Lake Forest
Carle Physician Group-Mattoon/Charleston, Mattoon
UC Comprehensive Cancer Center at Silver Cross, New Lenox
Cancer Care Center of O'Fallon, O'Fallon
HSHS Saint Elizabeth's Hospital, O'Fallon
Northwestern Medicine Oak Brook, Oak Brook
Northwestern Medicine Orland Park, Orland Park
University of Chicago Medicine-Orland Park, Orland Park
UW Health Carbone Cancer Center Rockford, Rockford
Southern Illinois University School of Medicine, Springfield
Springfield Clinic, Springfield
Springfield Memorial Hospital, Springfield
Carle Cancer Center, Urbana
The Carle Foundation Hospital, Urbana
Northwestern Medicine Cancer Center Warrenville, Warrenville
IndianaUChicago Medicine Northwest Indiana, Crown Point
Franciscan Health Indianapolis, Indianapolis
Franciscan Health Mooresville, Mooresville
IowaMary Greeley Medical Center, Ames
McFarland Clinic - Ames, Ames
UI Health Care Mission Cancer and Blood - Ankeny Clinic, Ankeny
UI Health Care Mission Cancer and Blood - West Des Moines Clinic, Clive
Iowa Methodist Medical Center, Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Waukee Clinic, Waukee
LouisianaLouisiana Hematology Oncology Associates LLC, Baton Rouge
Mary Bird Perkins Cancer Center, Baton Rouge
Mary Bird Perkins Cancer Center - Metairie, Metairie
MassachusettsBrigham and Women's Hospital, Boston
Dana-Farber Cancer Institute, Boston
Massachusetts General Hospital Cancer Center, Boston
MichiganTrinity Health Saint Joseph Mercy Hospital Ann Arbor, Ann Arbor
University of Michigan Rogel Cancer Center, Ann Arbor
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton
Trinity Health Medical Center - Brighton, Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton, Canton
Trinity Health Medical Center - Canton, Canton
Chelsea Hospital, Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital, Chelsea
Corewell Health Dearborn Hospital, Dearborn
Corewell Health Farmington Hills Hospital, Farmington Hills
University of Michigan Health - Sparrow Lansing, Lansing
Trinity Health Saint Mary Mercy Livonia Hospital, Livonia
Corewell Health William Beaumont University Hospital, Royal Oak
Corewell Health Beaumont Troy Hospital, Troy
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti
MinnesotaSanford Joe Lueken Cancer Center, Bemidji
Essentia Health Saint Joseph's Medical Center, Brainerd
Minnesota Oncology Hematology PA-Chaska, Chaska
Essentia Health - Deer River Clinic, Deer River
Essentia Health Cancer Center, Duluth
Essentia Health Saint Mary's Medical Center, Duluth
Miller-Dwan Hospital, Duluth
Fairview Southdale Hospital, Edina
Essentia Health Hibbing Clinic, Hibbing
Fairview Clinics and Surgery Center Maple Grove, Maple Grove
Abbott-Northwestern Hospital, Minneapolis
Hennepin County Medical Center, Minneapolis
University of Minnesota/Masonic Cancer Center, Minneapolis
Mayo Clinic in Rochester, Rochester
Regions Hospital, Saint Paul
Essentia Health Sandstone, Sandstone
Saint Francis Regional Medical Center, Shakopee
Lakeview Hospital, Stillwater
Essentia Health Virginia Clinic, Virginia
Ridgeview Medical Center, Waconia
MissouriSaint Francis Medical Center, Cape Girardeau
MU Health - University Hospital/Ellis Fischel Cancer Center, Columbia
Mercy Hospital Springfield, Springfield
Mercy Hospital Saint Louis, St Louis
Mercy Hospital South, St Louis
NebraskaNebraska Medicine-Bellevue, Bellevue
Nebraska Medicine-Village Pointe, Omaha
University of Nebraska Medical Center, Omaha
New JerseyMemorial Sloan Kettering Basking Ridge, Basking Ridge
Cooper Hospital University Medical Center, Camden
Memorial Sloan Kettering Monmouth, Middletown
Memorial Sloan Kettering Bergen, Montvale
Cooper CyberKnife Center, Mount Laurel
New MexicoLovelace Medical Center-Saint Joseph Square, Albuquerque
Lovelace Radiation Oncology, Albuquerque
New YorkNorthwell Health Imbert Cancer Center, Bay Shore
Memorial Sloan Kettering Commack, Commack
Glens Falls Hospital, Glens Falls
Northwell Health Cancer Institute at Huntington, Greenlawn
Memorial Sloan Kettering Westchester, Harrison
Northwell Health/Center for Advanced Medicine, Lake Success
Northern Westchester Hospital, Mount Kisco
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York
Lenox Hill Hospital, New York
Manhattan Eye Ear and Throat Hospital, New York
Memorial Sloan Kettering Cancer Center, New York
Phelps Memorial Hospital Center, Sleepy Hollow
Memorial Sloan Kettering Nassau, Uniondale
North CarolinaDuke Cancer Center Cary, Cary
UNC Lineberger Comprehensive Cancer Center, Chapel Hill
Atrium Health Pineville/LCI-Pineville, Charlotte
Atrium Health University City/LCI-University, Charlotte
Carolinas Medical Center/Levine Cancer Institute, Charlotte
Levine Cancer Institute-Ballantyne, Charlotte
Wake Forest University at Clemmons, Clemmons
Atrium Health Cabarrus/LCI-Concord, Concord
Duke University Medical Center, Durham
Levine Cancer Institute-Gaston, Gastonia
Hayworth Cancer Center, High Point
Atrium Health Union/LCI-Union, Monroe
Duke Cancer Center Raleigh, Raleigh
Wake Forest Baptist Health - Wilkes Medical Center, Wilkesboro
Wake Forest University Health Sciences, Winston-Salem
North DakotaSanford Bismarck Medical Center, Bismarck
Sanford Broadway Medical Center, Fargo
Sanford Roger Maris Cancer Center, Fargo
OhioUH Seidman Cancer Center at UH Avon Health Center, Avon
UHHS-Chagrin Highlands Medical Center, Beachwood
Miami Valley Hospital South, Centerville
University of Cincinnati Cancer Center-UC Medical Center, Cincinnati
Case Western Reserve University, Cleveland
Ohio State University Comprehensive Cancer Center, Columbus
Miami Valley Hospital, Dayton
Miami Valley Hospital North, Dayton
Premier Blood and Cancer Center, Dayton
Atrium Medical Center-Middletown Regional Hospital, Franklin
Miami Valley Cancer Care and Infusion, Greenville
UH Seidman Cancer Center at Lake Health Mentor Campus, Mentor
University Hospitals Parma Medical Center, Parma
University Hospitals Portage Medical Center, Ravenna
Upper Valley Medical Center, Troy
University of Cincinnati Cancer Center-West Chester, West Chester
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
Oklahoma Cancer Specialists and Research Institute-Tulsa, Tulsa
PennsylvaniaLehigh Valley Hospital-Cedar Crest, Allentown
UPMC-Heritage Valley Health System Beaver, Beaver
Lehigh Valley Hospital - Muhlenberg, Bethlehem
Carlisle Regional Cancer Center, Carlisle
Christiana Care Health System-Concord Health Center, Chadds Ford
Geisinger Medical Center, Danville
Saint Vincent Hospital, Erie
UPMC Hillman Cancer Center Erie, Erie
UPMC Cancer Center at UPMC Horizon, Farrell
UPMC Cancer Centers - Arnold Palmer Pavilion, Greensburg
UPMC Pinnacle Cancer Center/Community Osteopathic Campus, Harrisburg
Geisinger Medical Center-Cancer Center Hazleton, Hazleton
Penn State Milton S Hershey Medical Center, Hershey
IRMC Cancer Center, Indiana
Jefferson Hospital, Jefferson Hills
Geisinger Medical Oncology-Lewisburg, Lewisburg
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion, Mechanicsburg
Forbes Hospital, Monroeville
UPMC Cancer Center - Monroeville, Monroeville
UPMC Hillman Cancer Center - Monroeville, Monroeville
UPMC Hillman Cancer Center - New Castle, New Castle
Allegheny General Hospital, Pittsburgh
UPMC-Magee Womens Hospital, Pittsburgh
UPMC-Passavant Hospital, Pittsburgh
UPMC-Saint Clair Hospital Cancer Center, Pittsburgh
UPMC-Saint Margaret, Pittsburgh
UPMC-Shadyside Hospital, Pittsburgh
University of Pittsburgh Cancer Institute (UPCI), Pittsburgh
West Penn Hospital, Pittsburgh
Geisinger Cancer Services-Pottsville, Pottsville
Community Medical Center, Scranton
UPMC Cancer Center at UPMC Northwest, Seneca
UPMC Cancer Center-Washington, Washington
UPMC Washington Hospital Radiation Oncology, Washington
Reading Hospital, West Reading
Wexford Health and Wellness Pavilion, Wexford
Geisinger Wyoming Valley/Henry Cancer Center, Wilkes-Barre
Divine Providence Hospital, Williamsport
UPMC Memorial, York
South CarolinaMedical University of South Carolina, Charleston
Self Regional Healthcare, Greenwood
South DakotaSanford Cancer Center Oncology Clinic, Sioux Falls
Sanford USD Medical Center - Sioux Falls, Sioux Falls
TexasParkland Memorial Hospital, Dallas
UT Southwestern Simmons Cancer Center - RedBird, Dallas
UT Southwestern/Simmons Cancer Center-Dallas, Dallas
UT Southwestern/Simmons Cancer Center-Fort Worth, Fort Worth
UT Southwestern Clinical Center at Richardson/Plano, Richardson
Scott and White Memorial Hospital, Temple
VermontCentral Vermont Medical Center/National Life Cancer Treatment, Berlin Corners
University of Vermont Medical Center, Burlington
University of Vermont and State Agricultural College, Burlington
VirginiaInova Alexandria Hospital, Alexandria
Inova Fair Oaks Hospital, Fairfax
Inova Schar Cancer Institute, Fairfax
Bon Secours Saint Francis Medical Center, Midlothian
Bon Secours Cancer Institute at Reynolds Crossing, Richmond
WashingtonVirginia Mason Medical Center, Seattle
West VirginiaEdwards Comprehensive Cancer Center, Huntington
WisconsinLanglade Hospital and Cancer Center, Antigo
Duluth Clinic Ashland, Ashland
Northwest Wisconsin Cancer Center, Ashland
Marshfield Medical Center-EC Cancer Center, Eau Claire
Saint Vincent Hospital Cancer Center Green Bay, Green Bay
Saint Vincent Hospital Cancer Center at Saint Mary's, Green Bay
Essentia Health-Hayward Clinic, Hayward
Gundersen Lutheran Medical Center, La Crosse
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center, Madison
University of Wisconsin Carbone Cancer Center - University Hospital, Madison
Marshfield Medical Center-Marshfield, Marshfield
Froedtert Menomonee Falls Hospital, Menomonee Falls
Medical College of Wisconsin, Milwaukee
Marshfield Medical Center - Minocqua, Minocqua
ProHealth D N Greenwald Center, Mukwonago
Cancer Center of Western Wisconsin, New Richmond
Drexel Town Square Health Center, Oak Creek
ProHealth Oconomowoc Memorial Hospital, Oconomowoc
Aspirus Cancer Care - James Beck Cancer Center, Rhinelander
Marshfield Medical Center-Rice Lake, Rice Lake
Saint Vincent Hospital Cancer Center at Sheboygan, Sheboygan
Essentia Health-Spooner Clinic, Spooner
Aspirus Cancer Care - Stevens Point, Stevens Point
Marshfield Medical Center-River Region at Stevens Point, Stevens Point
Saint Vincent Hospital Cancer Center at Sturgeon Bay, Sturgeon Bay
Essentia Health Saint Mary's Hospital - Superior, Superior
UW Cancer Center at ProHealth Care, Waukesha
Aspirus Regional Cancer Center, Wausau
Froedtert West Bend Hospital/Kraemer Cancer Center, West Bend
Marshfield Medical Center - Weston, Weston
Aspirus Cancer Care - Wisconsin Rapids, Wisconsin Rapids

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.