Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial
- Conditions
- Metastatic Clear Cell Renal Cell CarcinomaMetastatic Renal Cell CarcinomaStage IV Renal Cell Cancer AJCC v8
- Interventions
- Procedure: Cytoreductive NephrectomyDrug: Active Comparator
- Registration Number
- NCT04510597
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.
- Detailed Description
PRIMARY OBJECTIVE:
I. To compare overall survival in participants with newly diagnosed metastatic renal cell carcinoma who are randomized to receive immune checkpoint inhibitor-based combination treatment plus cytoreductive nephrectomy versus immune checkpoint inhibitor-based combination treatment alone.
SECONDARY OBJECTIVES:
I. To compare overall survival between arms in the subset who received their assigned protocol treatment.
II. To assess complications of nephrectomy and post-randomization drug toxicities.
III. To compare objective response rate in metastatic sites between the arms in participants with measurable metastatic disease.
IV. To assess change in diameter of primary tumor at week 12 disease assessment in participants who have received pre-randomization treatment.
BANKING OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE:
PRE-RANDOMIZATION TREATMENT: Treatment naive patients are assigned to 1 of 3 treatment regimens per standard of care.
REGIMEN I: Patients receive nivolumab intravenously (IV) and ipilimumab IV. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1. Cycles repeat every 2-4 weeks in the absence of disease progression or unacceptable toxicity.
REGIMEN II: Patients receive pembrolizumab IV on day 1 and axitinib orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
REGIMEN III: Patients receive avelumab IV on day 1 and axitinib PO BID on days 1-14. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: Some patients may have already completed the standard of care pre-randomization treatment specified above off-trial.
RANDOMIZATION TREATMENT: Between 10-14 weeks from the start of on-trial or off-trial pre-randomization treatment, patients are randomized to 1 of 2 arms.
ARM I: Patients receive nivolumab IV, pembrolizumab IV, or avelumab IV on day 1. Patients also receive axitinib PO BID. Cycles with nivolumab repeat every 2 or 4 weeks, cycles with pembrolizumab repeat every 3 weeks, and cycles with avelumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Within 42 days following randomization, patients undergo radical or partial nephrectomy in addition to nivolumab, pembrolizumab, avelumab, and axitinib as in Arm I in the absence of disease progression or unacceptable toxicity. Axitinib should be stopped at least 24 hours prior to surgery.
After completion of trial treatment, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, and then annually for up to 7 years from randomization.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 364
-
STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
-
STEP 1 REGISTRATION: Participants must have primary tumor in place
-
STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
- Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
- CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast
Scans must be performed within the following timeframes:
-
Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
-
Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
- STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
- STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
- STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
- STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
- STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
- STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
-
CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
-
CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2
• STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
-
Stable disease
-
Partial response
-
The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
- STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
- STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
- STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
-
2 infusions of nivolumab + 1 infusion of ipilimumab
-
2 infusions of pembrolizumab
-
2 infusions of avelumab
- STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
- STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
- STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
- STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
- STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
- STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
- STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
-
STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
-
STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
- Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
- Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
-
STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
-
Treatment naive participants must not have received any pre-randomization treatment.
-
Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
- 4 infusions of nivolumab
- 4 infusions of ipilimumab
- 4 infusions of pembrolizumab
- 7 infusions of avelumab
-
-
STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
- Treatment naive participants must not have received any immunotherapy within a year of registration
- Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
-
STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
-
STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
-
STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
-
STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
-
STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
-
STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Continued Systemic Therapy Only Cytoreductive Nephrectomy Nivolumab 240 mg IV 1 q 2 weeks OR Nivolumab 480 mg IV 1 q 4 weeks OR Pembrolizumab 200 mg IV 1 q 3 weeks Axitinib 5 mg oral Daily BID OR Avelumab 10 mg/kg IV 1 q 2 weeks Axitinib 5 mg oral Daily BID Arm 1: Continued Systemic Therapy Only Active Comparator Nivolumab 240 mg IV 1 q 2 weeks OR Nivolumab 480 mg IV 1 q 4 weeks OR Pembrolizumab 200 mg IV 1 q 3 weeks Axitinib 5 mg oral Daily BID OR Avelumab 10 mg/kg IV 1 q 2 weeks Axitinib 5 mg oral Daily BID Arm 2: Nephrectomy and Continued Systemic Therapy Cytoreductive Nephrectomy Continued systemic therapy as above, plus: Radical or partial nephrectomy may be performed using laparoscopic, open, or robotic approaches. Surgery should be performed within 8 weeks of randomization.
- Primary Outcome Measures
Name Time Method Overall survival From date of randomization to date of death due to any cause, assessed up to 7 years. Analysis will be intent-to-treat. Evidence suggesting early termination of the trial and a conclusion that the cytoreductive nephrectomy (CN) approach is superior to treatment alone would be if the null hypothesis is rejected at the one-sided 0.005 level. For the second and third interim analyses, the null and alternative hypotheses with respect to survival will be tested, with superiority tested at the one-sided 0.005 level, and futility determined to be met if the (CN versus no CN) hazard ratio is greater than or equal to 1. A proportional hazards model will be fit to estimate the hazard ratio adjusting for the stratification factors as covariates in the model. Will evaluate whether each of the stratification factors are predictive factors of cytoreductive nephrectomy by placing an interaction term corresponding to each stratification factor and treatment arm in the proportional hazards survival model.
- Secondary Outcome Measures
Name Time Method Overall survival in subset who received assigned protocol treatment From date of randomization to date of death due to any cause, assessed up to 7 years Will be included in the proportional hazards regression model adjusting for stratification factors as covariates.
Change in maximum diameter of primary tumor From the disease assessment just prior to the start of immunotherapy to the week 12 disease assessment Descriptive statistics will be provided including stratified results by treatment regimen received. Potential additional analyses may include assessment of the interaction between change in primary tumor and randomized treatment arm. This will be modeled as an interaction term in the proportional hazards survival model.
Progression-free survival From date of randomization to date of first documentation of progression, or death due to any cause, assessed up to 7 years A proportional hazards model will be used to compare progression-free survival between arms, adjusting for the stratification factors as covariates.
Objective response Up to 7 years Objective response includes all confirmed and unconfirmed partial and complete responses. Baseline will be disease assessment at randomization. Response Evaluation Criteria in Solid Tumors response rates will be evaluated, excluding the primary tumor in the kidney because that disease will be removed in half the participant's post-randomization. Comparison of response rates will be performed using logistic regression with stratification factors as covariates and an indicator for treatment arm.
Trial Locations
- Locations (386)
University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Kingman Regional Medical Center
🇺🇸Kingman, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸Cameron Park, California, United States
Keck Medicine of USC Buena Park
🇺🇸Buena Park, California, United States
Keck Medicine of USC Huntington Beach
🇺🇸Huntington Beach, California, United States
Eden Hospital Medical Center
🇺🇸Castro Valley, California, United States
Saint Anthony's Health
🇺🇸Alton, Illinois, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
AdventHealth Kissimmee
🇺🇸Kissimmee, Florida, United States
Sutter Davis Hospital
🇺🇸Davis, California, United States
Palo Alto Medical Foundation-Fremont
🇺🇸Fremont, California, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸Roseville, California, United States
City of Hope South Pasadena
🇺🇸South Pasadena, California, United States
SIH Cancer Institute
🇺🇸Carterville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Palo Alto Medical Foundation-Gynecologic Oncology
🇺🇸Mountain View, California, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
AdventHealth Celebration
🇺🇸Celebration, Florida, United States
AMG Crystal Lake - Oncology
🇺🇸Crystal Lake, Illinois, United States
Advocate Good Samaritan Hospital
🇺🇸Downers Grove, Illinois, United States
Palo Alto Medical Foundation-Camino Division
🇺🇸Mountain View, California, United States
Advocate Sherman Hospital
🇺🇸Elgin, Illinois, United States
Loyola Center for Health at Burr Ridge
🇺🇸Burr Ridge, Illinois, United States
Palo Alto Medical Foundation Health Care
🇺🇸Palo Alto, California, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Saint Mary's Hospital
🇺🇸Centralia, Illinois, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
AdventHealth Winter Park
🇺🇸Winter Park, Florida, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
AdventHealth Altamonte
🇺🇸Altamonte Springs, Florida, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Edward Hospital/Cancer Center?Plainfield
🇺🇸Plainfield, Illinois, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
AMG Libertyville - Oncology
🇺🇸Libertyville, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Trinity Regional Medical Center
🇺🇸Fort Dodge, Iowa, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Capital Region Southwest Campus
🇺🇸Jefferson City, Missouri, United States
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Gulfport Memorial Hospital
🇺🇸Gulfport, Mississippi, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Phelps Memorial Hospital Center
🇺🇸Sleepy Hollow, New York, United States
Radiation Oncology Associates
🇺🇸Reno, Nevada, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸Jacksonville, North Carolina, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Armes Family Cancer Center
🇺🇸Findlay, Ohio, United States
Saint Elizabeth Boardman Hospital
🇺🇸Boardman, Ohio, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Beachwood, Ohio, United States
UPMC Altoona
🇺🇸Altoona, Pennsylvania, United States
UPMC Hillman Cancer Center - Monroeville
🇺🇸Monroeville, Pennsylvania, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸Clinton, North Carolina, United States
UH Seidman Cancer Center at UH Avon Health Center
🇺🇸Avon, Ohio, United States
IRMC Cancer Center
🇺🇸Indiana, Pennsylvania, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Orion Cancer Care
🇺🇸Findlay, Ohio, United States
Indu and Raj Soin Medical Center
🇺🇸Beavercreek, Ohio, United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
🇺🇸Johnstown, Pennsylvania, United States
UPMC Hillman Cancer Center - Part of Frick Hospital
🇺🇸Mount Pleasant, Pennsylvania, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸Franklin, Ohio, United States
Dayton Physician LLC-Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸Goldsboro, North Carolina, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸Mentor, Ohio, United States
Dayton Physicians LLC-Miami Valley South
🇺🇸Centerville, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
🇺🇸Greensburg, Pennsylvania, United States
Dayton Physicians LLC-Wayne
🇺🇸Greenville, Ohio, United States
UPMC Cancer Center-Uniontown
🇺🇸Uniontown, Pennsylvania, United States
UPMC-Heritage Valley Health System Beaver
🇺🇸Beaver, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
UPMC Hillman Cancer Center Erie
🇺🇸Erie, Pennsylvania, United States
Rogue Valley Medical Center
🇺🇸Medford, Oregon, United States
Arnold Palmer Cancer Center Medical Oncology Norwin
🇺🇸N. Huntingdon, Pennsylvania, United States
UPMC Cancer Center-Natrona Heights
🇺🇸Natrona Heights, Pennsylvania, United States
Prisma Health Cancer Institute - Easley
🇺🇸Easley, South Carolina, United States
Vince Lombardi Cancer Clinic - Oshkosh
🇺🇸Oshkosh, Wisconsin, United States
UPMC Cancer Center at UPMC Horizon
🇺🇸Farrell, Pennsylvania, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Overlake Medical Center
🇺🇸Bellevue, Washington, United States
Aurora Cancer Care-Grafton
🇺🇸Grafton, Wisconsin, United States
UT Southwestern Simmons Cancer Center - RedBird
🇺🇸Dallas, Texas, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸Yakima, Washington, United States
Marshfield Clinic-Wausau Center
🇺🇸Wausau, Wisconsin, United States
Aurora Health Care Germantown Health Center
🇺🇸Germantown, Wisconsin, United States
Aurora BayCare Medical Center
🇺🇸Green Bay, Wisconsin, United States
Aurora Cancer Care-Southern Lakes VLCC
🇺🇸Burlington, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
UPMC Cancer Center-Washington
🇺🇸Washington, Pennsylvania, United States
UPMC Cancer Center at UPMC Northwest
🇺🇸Seneca, Pennsylvania, United States
Aurora Cancer Care-Kenosha South
🇺🇸Kenosha, Wisconsin, United States
Prisma Health Cancer Institute - Butternut
🇺🇸Greenville, South Carolina, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
UPMC West Mifflin-Cancer Center Jefferson
🇺🇸West Mifflin, Pennsylvania, United States
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
UT Southwestern Clinical Center at Richardson/Plano
🇺🇸Richardson, Texas, United States
Norris Cotton Cancer Center-North
🇺🇸Saint Johnsbury, Vermont, United States
Marshfield Clinic-Chippewa Center
🇺🇸Chippewa Falls, Wisconsin, United States
Marshfield Clinic - Ladysmith Center
🇺🇸Ladysmith, Wisconsin, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
🇺🇸West Bend, Wisconsin, United States
Los Angeles County-USC Medical Center
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Advocate Illinois Masonic Medical Center
🇺🇸Chicago, Illinois, United States
UPMC-Shadyside Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Passavant Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC-Saint Clair Hospital Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Ben Taub General Hospital
🇺🇸Houston, Texas, United States
Las Vegas Urology - Pecos
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Smoke Ranch
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada-Summerlin
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Charleston
🇺🇸Las Vegas, Nevada, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Las Vegas Prostate Cancer Center
🇺🇸Las Vegas, Nevada, United States
Ann M Wierman MD LTD
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at MountainView
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Sunset
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Fort Apache
🇺🇸Las Vegas, Nevada, United States
University Cancer Center
🇺🇸Las Vegas, Nevada, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸Cincinnati, Ohio, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Utah Sugarhouse Health Center
🇺🇸Salt Lake City, Utah, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
George E Wahlen Department of Veterans Affairs Medical Center
🇺🇸Salt Lake City, Utah, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Kaiser Permanente Northwest
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Cambridge Medical Center
🇺🇸Cambridge, Minnesota, United States
Fairview Northland Medical Center
🇺🇸Princeton, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
UPMC Cancer Center at UPMC McKeesport
🇺🇸McKeesport, Pennsylvania, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Las Vegas Cancer Center-Medical Center
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
Hope Cancer Care of Nevada-Pahrump
🇺🇸Pahrump, Nevada, United States
Saint Mary's Regional Medical Center
🇺🇸Reno, Nevada, United States
Aurora Bay Area Medical Group-Marinette
🇺🇸Marinette, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Keck Medicine of USC Koreatown
🇺🇸Los Angeles, California, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸Auburn, California, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
USC Norris Oncology/Hematology-Newport Beach
🇺🇸Newport Beach, California, United States
Sutter Cancer Research Consortium
🇺🇸Novato, California, United States
Advocate Good Shepherd Hospital
🇺🇸Barrington, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
🇺🇸Melrose Park, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
Dayton Physicians LLC - Troy
🇺🇸Troy, Ohio, United States
Springfield Regional Cancer Center
🇺🇸Springfield, Ohio, United States
Springfield Regional Medical Center
🇺🇸Springfield, Ohio, United States
Saint Joseph Warren Hospital
🇺🇸Warren, Ohio, United States
Saint Elizabeth Youngstown Hospital
🇺🇸Youngstown, Ohio, United States
Kaiser Sunnyside Medical Center
🇺🇸Clackamas, Oregon, United States
UPMC Hillman Cancer Center at Butler Health System
🇺🇸Butler, Pennsylvania, United States
Aurora Cancer Care-Milwaukee
🇺🇸Milwaukee, Wisconsin, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Aurora Sinai Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
Vince Lombardi Cancer Clinic-Sheboygan
🇺🇸Sheboygan, Wisconsin, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Comprehensive Cancer Centers of Nevada - Town Center
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Fort Apache
🇺🇸Las Vegas, Nevada, United States
Illinois CancerCare-Dixon
🇺🇸Dixon, Illinois, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
🇺🇸Omaha, Nebraska, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Oncology Associates PC
🇺🇸Omaha, Nebraska, United States
University of Rochester
🇺🇸Rochester, New York, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
PCR Oncology
🇺🇸Arroyo Grande, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Keck Medical Center of USC Pasadena
🇺🇸Pasadena, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
Palo Alto Medical Foundation-Santa Cruz
🇺🇸Santa Cruz, California, United States
Mills Health Center
🇺🇸San Mateo, California, United States
Sutter Pacific Medical Foundation
🇺🇸Santa Rosa, California, United States
City of Hope Upland
🇺🇸Upland, California, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
🇺🇸Vacaville, California, United States
Cedars-Sinai Cancer - Tarzana
🇺🇸Tarzana, California, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Elmhurst Memorial Hospital
🇺🇸Elmhurst, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Advocate South Suburban Hospital
🇺🇸Hazel Crest, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Loyola Medicine Homer Glen
🇺🇸Homer Glen, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Condell Memorial Hospital
🇺🇸Libertyville, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸Naperville, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
University of Chicago Medicine-Orland Park
🇺🇸Orland Park, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
Reid Health
🇺🇸Richmond, Indiana, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
Saint Anthony Regional Hospital
🇺🇸Carroll, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Broadlawns Medical Center
🇺🇸Des Moines, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
Methodist West Hospital
🇺🇸West Des Moines, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Hematology/Oncology Clinic PLLC
🇺🇸Baton Rouge, Louisiana, United States
LSU Healthcare Network / Metairie Multi-Specialty Clinic
🇺🇸Metairie, Louisiana, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
University of Michigan - Brighton Center for Specialty Care
🇺🇸Brighton, Michigan, United States
East Jefferson General Hospital
🇺🇸Metairie, Louisiana, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Cancer Institute-Downriver
🇺🇸Brownstown, Michigan, United States
Henry Ford Macomb Hospital-Clinton Township
🇺🇸Clinton Township, Michigan, United States
Henry Ford Hematology Oncology - Hayes
🇺🇸Clinton Township, Michigan, United States
Henry Ford Medical Center-Fairlane
🇺🇸Dearborn, Michigan, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Ascension Borgess Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Lakeland Hospital Niles
🇺🇸Niles, Michigan, United States
Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Lakeland Medical Center Saint Joseph
🇺🇸Saint Joseph, Michigan, United States
Spectrum Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Henry Ford Medical Center-Columbus
🇺🇸Novi, Michigan, United States
Henry Ford Macomb Health Center - Shelby Township
🇺🇸Shelby, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
Henry Ford Wyandotte Hospital
🇺🇸Wyandotte, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Missouri Baptist Outpatient Center-Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
Carson Tahoe Regional Medical Center
🇺🇸Carson City, Nevada, United States
Cancer and Blood Specialists-Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Horizon Ridge
🇺🇸Henderson, Nevada, United States
Las Vegas Cancer Center-Henderson
🇺🇸Henderson, Nevada, United States
OptumCare Cancer Care at Seven Hills
🇺🇸Henderson, Nevada, United States
GenesisCare USA - Henderson
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Pebble
🇺🇸Henderson, Nevada, United States
Desert West Surgery
🇺🇸Las Vegas, Nevada, United States
Hope Cancer Care of Nevada
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Central
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Las Vegas
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Southwest
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Cathedral Rock
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Vegas Tenaya
🇺🇸Las Vegas, Nevada, United States
UPMC-Saint Margaret
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Hillman Cancer Center - New Castle
🇺🇸New Castle, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, South Carolina, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
🇺🇸Fort Worth, Texas, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Valley Medical Center
🇺🇸Renton, Washington, United States
Froedtert Menomonee Falls Hospital
🇺🇸Menomonee Falls, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Aurora Medical Center in Summit
🇺🇸Summit, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Aurora Cancer Care-Racine
🇺🇸Racine, Wisconsin, United States
Aurora West Allis Medical Center
🇺🇸West Allis, Wisconsin, United States
Drexel Town Square Health Center
🇺🇸Oak Creek, Wisconsin, United States
Vince Lombardi Cancer Clinic-Two Rivers
🇺🇸Two Rivers, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Aurora Cancer Care-Milwaukee West
🇺🇸Wauwatosa, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Comprehensive Cancer Centers of Nevada-Southeast Henderson
🇺🇸Henderson, Nevada, United States
Urology Specialists of Nevada - Green Valley
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Green Valley
🇺🇸Henderson, Nevada, United States
AdventHealth Medical Group Urology at Orlando
🇺🇸Orlando, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
AdventHealth East Orlando
🇺🇸Orlando, Florida, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Louisiana State University Health Science Center
🇺🇸New Orleans, Louisiana, United States