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

Phase 2

Recruiting

• Conditions: Metastatic Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Unresectable Renal Cell Carcinoma
• Interventions: Biological: Avelumab; Drug: Axitinib; Drug: Cabozantinib; Biological: Ipilimumab; Drug: Lenvatinib; Biological: Nivolumab; Biological: Pembrolizumab; Radiation: Stereotactic Ablative Radiotherapy

• Registration Number: NCT05327686
• Lead Sponsor: NRG Oncology

Brief Summary

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 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.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine whether the addition of stereotactic ablative radiotherapy (SABR) to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC). The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria.

SECONDARY OBJECTIVES:

I. To assess the safety, toxicity and tolerability of the two treatment strategies as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5 in each treatment arm.

II. To assess the objective response rate (ORR) by Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) in each treatment arm.

III. Nephrectomy and radiographic progression-free survival excluding nephrectomies that were performed for non-protocol specified indications (nephrectomy and radiographic progression-free survival \[nrPFS\]2).

IV. Radiographic progression-free survival (rPFS). V. To assess overall survival (OS) in each treatment arm. VI. To assess the time to subsequent second-line therapy or death in each treatment arm.

VII. To assess the rate of cytoreductive nephrectomy in each treatment arm. VIII. To assess treatment-free survival in patients who discontinue therapy for reason other than radiographic disease progression.

IX. To assess the ORR by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and iRECIST in the primary renal mass.

EXPLORATORY OBJECTIVES:

I. To assess composite nrPFS in the predefined histological subgroups below:

Ia. Clear cell versus non-clear cell histology. Ib. International Metastatic RCC database consortium (IMDC) intermediate versus poor risk group.

Ic. Systemic treatment with immunotherapy-immunotherapy combination versus immunotherapy-vascular endothelial growth factor (VEGF) targeted therapy combination.

Id. Sarcomatoid versus non sarcomatoid variant. II. To identify prognostic and predictive biomarkers of response to SABR in the context of immunotherapy based treatment via assessment of tissue and blood based biomarkers.

III. To evaluate the abscopal effect of SABR with systemic therapy. IIIa. Compare ORR in non-irradiated target lesions in the control arm patients undergoing immunotherapy alone to the experimental arm undergoing SABR + immunotherapy.

IV. To evaluate the impact of treatment on level of inferior vena cava (IVC) thrombus.

V. To compare accruing center identified iRECIST progression and centrally identified iRECIST progression events on computed tomography (CT).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib orally (PO) twice daily (BID); avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO once daily (QD); OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.

After completion of study treatment, patients are followed up every 6 months for 5 years, and then annually for 3 years.

Study Timeline

• Study First Submitted: 2022-04-07
• Study First Submitted QC: 2022-04-07
• Study First Posted: 2022-04-14
• Study Start: 2022-06-30
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-23
• Primary Completion: 2028-06-15
• Study Completion: 2032-06-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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)

  • 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (standard of care immunotherapy)	Nivolumab	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm I (standard of care immunotherapy)	Pembrolizumab	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm II (SABR, standard of care immunotherapy)	Avelumab	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm II (SABR, standard of care immunotherapy)	Pembrolizumab	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm II (SABR, standard of care immunotherapy)	Stereotactic Ablative Radiotherapy	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm II (SABR, standard of care immunotherapy)	Nivolumab	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm I (standard of care immunotherapy)	Ipilimumab	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm II (SABR, standard of care immunotherapy)	Ipilimumab	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm I (standard of care immunotherapy)	Avelumab	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm I (standard of care immunotherapy)	Axitinib	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm I (standard of care immunotherapy)	Cabozantinib	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm I (standard of care immunotherapy)	Lenvatinib	Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity.
Arm II (SABR, standard of care immunotherapy)	Cabozantinib	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm II (SABR, standard of care immunotherapy)	Axitinib	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.
Arm II (SABR, standard of care immunotherapy)	Lenvatinib	Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I.

Primary Outcome Measures

Name	Time	Method
Nephrectomy and radiographic progression-free survival (nrPFS)	From randomization to last follow-up, up to 8 years	Nephrectomy and radiographic progression-free survival time is defined as time from randomization to the date of first radiographic progression, nephrectomy, death, or last negative evaluation (censored). nrPFS rates are estimated using the Kaplan-Meier method. Progression is determined by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria modified for immunotherapy trials (iRECIST).

Secondary Outcome Measures

Name	Time	Method
Second-line therapy-free survival	From randomization to last follow-up, up to 8 years	Second-line therapy-free survival time is defined as time from randomization to the date of the initiation of second-line therapy, death, or last known follow-up (censored). Second-line therapy-free survival rates are estimated using the Kaplan-Meier method.
Percentage of participants with complete or partial response	From randomization to last follow-up, up to 8 years	Best overall response is determined by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria modified for immunotherapy trials (iRECIST).
Percentage of participants with complete or partial response in the primary renal mass	From randomization to last follow-up, up to 8 years	Best overall response is determined by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria modified for immunotherapy trials (iRECIST).
Radiographic progression-free survival (rPFS)	From randomization to last follow-up, up to 8 years	Radiographic progression-free survival time is defined as time from randomization to the date of first radiographic progression, death, or last negative evaluation (censored). rPFS rates are estimated using the Kaplan-Meier method. Radiographic progression is determined by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria modified for immunotherapy trials (iRECIST).
Nephrectomy and radiographic progression-free survival excluding nephrectomies that were performed for non-protocol specified reasons (nrPFS2)	From randomization to last follow-up, up to 8 years	Nephrectomy and radiographic progression-free survival time (excluding nephrectomies that were performed for non-protocol specified reasons) is defined as time from randomization to the date of first radiographic progression, nephrectomy performed for protocol-stated reasons, death, or last negative evaluation (censored). nrPFS2 rates are estimated using the Kaplan-Meier method. Progression is determined by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria modified for immunotherapy trials (iRECIST).
Overall survival	From randomization to last follow-up, up to 8 years	Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Percentage of participants who undergo cytoreductive nephrectomy	From randomization to last follow-up, up to 8 years
Treatment-free survival	From randomization to last follow-up, up to 8 years	Treatment-free survival time is defined as time from the discontinuation of protocol therapy to the date of death or last follow-up (censored). Treatment-free survival rates are estimated using the Kaplan-Meier method.
Percentage of participants with grade 3+ and with grade 4+ treatment-related adverse events	From randomization to last follow-up, up to 8 years	Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grades adverse event severity from 1=mild to 5=death. Adverse events recorded as possibly, probably, or definitely related to protocol treatment will be considered to be treatment-related.

Trial Locations

Locations (208)

Central Maryland Radiation Oncology in Howard County; 🇺🇸 Columbia, Maryland, United States

UM Baltimore Washington Medical Center/Tate Cancer Center; 🇺🇸 Glen Burnie, Maryland, United States

Beverly Hospital; 🇺🇸 Beverly, Massachusetts, United States

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Premier Blood and Cancer Center; 🇺🇸 Dayton, Ohio, United States

Dayton Physician LLC - Englewood; 🇺🇸 Dayton, Ohio, United States

Miami Valley Hospital North; 🇺🇸 Dayton, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital; 🇺🇸 Franklin, Ohio, United States

University of Pittsburgh Cancer Institute (UPCI); 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Northwestern Medicine Grayslake Outpatient Center; 🇺🇸 Grayslake, Illinois, United States

Northwestern Medicine Lake Forest Hospital; 🇺🇸 Lake Forest, Illinois, United States

Carle Physician Group-Mattoon/Charleston; 🇺🇸 Mattoon, Illinois, United States

Mills-Peninsula Medical Center; 🇺🇸 Burlingame, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

UC San Diego Health System - Encinitas; 🇺🇸 Encinitas, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Memorial Medical Center; 🇺🇸 Modesto, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville; 🇺🇸 Roseville, California, United States

Sutter Roseville Medical Center; 🇺🇸 Roseville, California, United States

Sutter Medical Center Sacramento; 🇺🇸 Sacramento, California, United States

UC San Diego Medical Center - Hillcrest; 🇺🇸 San Diego, California, United States

Pacific Central Coast Health Center-San Luis Obispo; 🇺🇸 San Luis Obispo, California, United States

Mills Health Center; 🇺🇸 San Mateo, California, United States

Ridley-Tree Cancer Center; 🇺🇸 Santa Barbara, California, United States

Sutter Pacific Medical Foundation; 🇺🇸 Santa Rosa, California, United States

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

Alton Memorial Hospital; 🇺🇸 Alton, Illinois, United States

Centralia Oncology Clinic; 🇺🇸 Centralia, Illinois, United States

Carle at The Riverfront; 🇺🇸 Danville, Illinois, United States

Cancer Care Specialists of Illinois - Decatur; 🇺🇸 Decatur, Illinois, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Northwestern Medicine Cancer Center Kishwaukee; 🇺🇸 DeKalb, Illinois, United States

Carle Physician Group-Effingham; 🇺🇸 Effingham, Illinois, United States

Crossroads Cancer Center; 🇺🇸 Effingham, Illinois, United States

Northwestern Medicine Cancer Center Delnor; 🇺🇸 Geneva, Illinois, United States

Northwestern Medicine Glenview Outpatient Center; 🇺🇸 Glenview, Illinois, United States

Cancer Care Center of O'Fallon; 🇺🇸 O'Fallon, Illinois, United States

HSHS Saint Elizabeth's Hospital; 🇺🇸 O'Fallon, Illinois, United States

UW Health Carbone Cancer Center Rockford; 🇺🇸 Rockford, Illinois, United States

Memorial Hospital East; 🇺🇸 Shiloh, Illinois, United States

Southern Illinois University School of Medicine; 🇺🇸 Springfield, Illinois, United States

Springfield Clinic; 🇺🇸 Springfield, Illinois, United States

Springfield Memorial Hospital; 🇺🇸 Springfield, Illinois, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

The Carle Foundation Hospital; 🇺🇸 Urbana, Illinois, United States

Northwestern Medicine Cancer Center Warrenville; 🇺🇸 Warrenville, Illinois, United States

Mary Greeley Medical Center; 🇺🇸 Ames, Iowa, United States

McFarland Clinic - Ames; 🇺🇸 Ames, Iowa, United States

Mission Cancer and Blood - Ankeny; 🇺🇸 Ankeny, Iowa, United States

Mission Cancer and Blood - West Des Moines; 🇺🇸 Clive, Iowa, United States

Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

Mission Cancer and Blood - Des Moines; 🇺🇸 Des Moines, Iowa, United States

Mission Cancer and Blood - Laurel; 🇺🇸 Des Moines, Iowa, United States

Louisiana Hematology Oncology Associates LLC; 🇺🇸 Baton Rouge, Louisiana, United States

Mary Bird Perkins Cancer Center; 🇺🇸 Baton Rouge, Louisiana, United States

Mary Bird Perkins Cancer Center - Metairie; 🇺🇸 Metairie, Louisiana, United States

East Jefferson General Hospital; 🇺🇸 Metairie, Louisiana, United States

LSU Healthcare Network / Metairie Multi-Specialty Clinic; 🇺🇸 Metairie, Louisiana, United States

Louisiana State University Health Science Center; 🇺🇸 New Orleans, Louisiana, United States

University Medical Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Touro Infirmary; 🇺🇸 New Orleans, Louisiana, United States

MaineHealth Coastal Cancer Treatment Center; 🇺🇸 Bath, Maine, United States

MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford; 🇺🇸 Biddeford, Maine, United States

Maine Medical Center-Bramhall Campus; 🇺🇸 Portland, Maine, United States

MaineHealth Cancer Care Center of York County; 🇺🇸 Sanford, Maine, United States

MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford; 🇺🇸 Sanford, Maine, United States

Maine Medical Center- Scarborough Campus; 🇺🇸 Scarborough, Maine, United States

Maine Medical Partners - South Portland; 🇺🇸 South Portland, Maine, United States

University of Maryland/Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Lahey Hospital and Medical Center; 🇺🇸 Burlington, Massachusetts, United States

Addison Gilbert Hospital; 🇺🇸 Gloucester, Massachusetts, United States

Lahey Medical Center-Peabody; 🇺🇸 Peabody, Massachusetts, United States

Winchester Hospital; 🇺🇸 Winchester, Massachusetts, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor; 🇺🇸 Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health Medical Center - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton; 🇺🇸 Canton, Michigan, United States

Trinity Health Medical Center - Canton; 🇺🇸 Canton, Michigan, United States

Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Corewell Health Dearborn Hospital; 🇺🇸 Dearborn, Michigan, United States

Corewell Health Farmington Hills Hospital; 🇺🇸 Farmington Hills, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Corewell Health William Beaumont University Hospital; 🇺🇸 Royal Oak, Michigan, United States

Corewell Health Beaumont Troy Hospital; 🇺🇸 Troy, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus; 🇺🇸 Ypsilanti, Michigan, United States

Sanford Joe Lueken Cancer Center; 🇺🇸 Bemidji, Minnesota, United States

Essentia Health Saint Joseph's Medical Center; 🇺🇸 Brainerd, Minnesota, United States

Essentia Health - Deer River Clinic; 🇺🇸 Deer River, Minnesota, United States

Essentia Health Cancer Center; 🇺🇸 Duluth, Minnesota, United States

Essentia Health Saint Mary's Medical Center; 🇺🇸 Duluth, Minnesota, United States

Miller-Dwan Hospital; 🇺🇸 Duluth, Minnesota, United States

Essentia Health Hibbing Clinic; 🇺🇸 Hibbing, Minnesota, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Essentia Health Sandstone; 🇺🇸 Sandstone, Minnesota, United States

Essentia Health Virginia Clinic; 🇺🇸 Virginia, Minnesota, United States

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

MU Health - University Hospital/Ellis Fischel Cancer Center; 🇺🇸 Columbia, Missouri, United States

Siteman Cancer Center at West County Hospital; 🇺🇸 Creve Coeur, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Mercy Hospital South; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center-South County; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Christian Hospital; 🇺🇸 Saint Louis, Missouri, United States

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

Nebraska Medicine-Bellevue; 🇺🇸 Bellevue, Nebraska, United States

Nebraska Medicine-Village Pointe; 🇺🇸 Omaha, Nebraska, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

Monmouth Medical Center Southern Campus; 🇺🇸 Lakewood, New Jersey, United States

Monmouth Medical Center; 🇺🇸 Long Branch, New Jersey, United States

Cooper CyberKnife Center; 🇺🇸 Mount Laurel, New Jersey, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Community Medical Center; 🇺🇸 Toms River, New Jersey, United States

Lovelace Medical Center-Saint Joseph Square; 🇺🇸 Albuquerque, New Mexico, United States

Lovelace Radiation Oncology; 🇺🇸 Albuquerque, New Mexico, United States

Glens Falls Hospital; 🇺🇸 Glens Falls, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone; 🇺🇸 New York, New York, United States

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

Sanford Bismarck Medical Center; 🇺🇸 Bismarck, North Dakota, United States

Sanford Broadway Medical Center; 🇺🇸 Fargo, North Dakota, United States

Sanford Roger Maris Cancer Center; 🇺🇸 Fargo, North Dakota, United States

UH Seidman Cancer Center at UH Avon Health Center; 🇺🇸 Avon, Ohio, United States

UHHS-Chagrin Highlands Medical Center; 🇺🇸 Beachwood, Ohio, United States

Dayton Physicians LLC-Miami Valley South; 🇺🇸 Centerville, Ohio, United States

Miami Valley Hospital South; 🇺🇸 Centerville, Ohio, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

Dayton Physicians LLC-Atrium; 🇺🇸 Franklin, Ohio, United States

Miami Valley Cancer Care and Infusion; 🇺🇸 Greenville, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

University Hospitals Parma Medical Center; 🇺🇸 Parma, Ohio, United States

University Hospitals Portage Medical Center; 🇺🇸 Ravenna, Ohio, United States

Upper Valley Medical Center; 🇺🇸 Troy, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Lehigh Valley Hospital-Cedar Crest; 🇺🇸 Allentown, Pennsylvania, United States

UPMC-Heritage Valley Health System Beaver; 🇺🇸 Beaver, Pennsylvania, United States

Lehigh Valley Hospital - Muhlenberg; 🇺🇸 Bethlehem, Pennsylvania, United States

Carlisle Regional Cancer Center; 🇺🇸 Carlisle, Pennsylvania, United States

UPMC Hillman Cancer Center Erie; 🇺🇸 Erie, Pennsylvania, United States

UPMC Cancer Centers - Arnold Palmer Pavilion; 🇺🇸 Greensburg, Pennsylvania, United States

UPMC Pinnacle Cancer Center/Community Osteopathic Campus; 🇺🇸 Harrisburg, Pennsylvania, United States

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion; 🇺🇸 Mechanicsburg, Pennsylvania, United States

UPMC Hillman Cancer Center - New Castle; 🇺🇸 New Castle, Pennsylvania, United States

UPMC-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Saint Margaret; 🇺🇸 Pittsburgh, Pennsylvania, 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

Reading Hospital; 🇺🇸 West Reading, Pennsylvania, United States

Divine Providence Hospital; 🇺🇸 Williamsport, Pennsylvania, United States

UPMC Memorial; 🇺🇸 York, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Sanford Cancer Center Oncology Clinic; 🇺🇸 Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Parkland Memorial Hospital; 🇺🇸 Dallas, Texas, United States

UT Southwestern Simmons Cancer Center - RedBird; 🇺🇸 Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas; 🇺🇸 Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Fort Worth; 🇺🇸 Fort Worth, Texas, United States

UT Southwestern Clinical Center at Richardson/Plano; 🇺🇸 Richardson, Texas, United States

Central Vermont Medical Center/National Life Cancer Treatment; 🇺🇸 Berlin, Vermont, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

University of Vermont and State Agricultural College; 🇺🇸 Burlington, Vermont, United States

West Virginia University Charleston Division; 🇺🇸 Charleston, West Virginia, United States

Edwards Comprehensive Cancer Center; 🇺🇸 Huntington, West Virginia, United States

Langlade Hospital and Cancer Center; 🇺🇸 Antigo, Wisconsin, United States

Duluth Clinic Ashland; 🇺🇸 Ashland, Wisconsin, United States

Northwest Wisconsin Cancer Center; 🇺🇸 Ashland, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center; 🇺🇸 Eau Claire, Wisconsin, United States

Essentia Health-Hayward Clinic; 🇺🇸 Hayward, Wisconsin, United States

Marshfield Medical Center - Ladysmith; 🇺🇸 Ladysmith, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center; 🇺🇸 Madison, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, United States

Froedtert Menomonee Falls Hospital; 🇺🇸 Menomonee Falls, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Marshfield Medical Center - Minocqua; 🇺🇸 Minocqua, Wisconsin, United States

ProHealth D N Greenwald Center; 🇺🇸 Mukwonago, Wisconsin, United States

Marshfield Medical Center - Neillsville; 🇺🇸 Neillsville, Wisconsin, United States

Drexel Town Square Health Center; 🇺🇸 Oak Creek, Wisconsin, United States

ProHealth Oconomowoc Memorial Hospital; 🇺🇸 Oconomowoc, Wisconsin, United States

Aspirus Cancer Care - James Beck Cancer Center; 🇺🇸 Rhinelander, Wisconsin, United States

Marshfield Medical Center-Rice Lake; 🇺🇸 Rice Lake, Wisconsin, United States

Essentia Health-Spooner Clinic; 🇺🇸 Spooner, Wisconsin, United States

Aspirus Cancer Care - Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Essentia Health Saint Mary's Hospital - Superior; 🇺🇸 Superior, Wisconsin, United States

UW Cancer Center at ProHealth Care; 🇺🇸 Waukesha, Wisconsin, United States

Aspirus Regional Cancer Center; 🇺🇸 Wausau, Wisconsin, United States

Froedtert West Bend Hospital/Kraemer Cancer Center; 🇺🇸 West Bend, Wisconsin, United States

Marshfield Medical Center - Weston; 🇺🇸 Weston, Wisconsin, United States

Aspirus Cancer Care - Wisconsin Rapids; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

Marshfield Clinic - Wisconsin Rapids Center; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

University Health Network-Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Beacon Hospital; 🇮🇪 Dublin, Co Dublin, Ireland

Saint Lukes Hospital; 🇮🇪 Dublin, Co Dublin, Ireland