A Study to Compare Treatments for a Type of Kidney Cancer Called TFE/Translocation Renal Cell Carcinoma (tRCC)

Phase 2

Active, not recruiting

• Conditions: Metastatic Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Unresectable Renal Cell Carcinoma; TFE3-Rearranged Renal Cell Carcinoma
• Interventions: Drug: Axitinib; Biological: Nivolumab

• Registration Number: NCT03595124
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase II trial studies how well axitinib and nivolumab work in treating patients with TFE/translocation renal cell carcinoma that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving axitinib and nivolumab may work better in treating patients with TFE/translocation renal cell carcinoma compared to standard treatment, including surgery, chemotherapy, or immunotherapy.

Detailed Description

PRIMARY OBJECTIVE:

I. To establish the clinical activity, assessed primarily by progression-free survival, of nivolumab therapy with or without axitinib for advanced transcription factor E3/translocation morphology renal cell carcinoma (TFE/tRCC).

SECONDARY OBJECTIVE:

I. To further define the toxicities of the study arms in the treatment of translocation morphology RCC across all ages.

EXPLORATORY OBJECTIVES:

I. To characterize tRCC clinical behavior across all age groups. II. To evaluate type of antitumor immune response and stability of T cell activation before and after treatment with immunotherapy or antiangiogenic therapy.

III. To develop a tumor bank of tRCC tumor samples treated on study for further biological investigations.

IV. To characterize the pharmacokinetics of axitinib when given in combination with nivolumab in pediatric patients with tRCC.

OUTLINE: Patients are now randomized to 1 of 2 arms - Arm A or Arm C.

ARM A: Patients receive axitinib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive axitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AS OF 1/23/2020 - PROSPECTIVE PATIENTS ARE RANDOMLY ASSIGNED TO ARMS A OR C)

ARM C: Patients receive nivolumab IV over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and every 6 months for 2 years. Follow-up at year 5 and beyond is at the discretion of the treating physician.

Study Timeline

• Study First Submitted: 2018-07-19
• Study First Submitted QC: 2018-07-19
• Study First Posted: 2018-07-23
• Study Start: 2019-01-08
• Primary Completion: 2024-09-30
• Status Verified: 2025-02
• Last Update Submitted: 2025-05-08
• Last Update Posted: 2025-05-09
• Study Completion: 2026-01-23

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Patients must be >= 12 months at enrollment

• Patients must have a body surface area (BSA) >= 0.53 m^2

• Histologically confirmed unresectable or metastatic translocation morphology renal cell carcinoma diagnosed using World Health Organization (WHO)-defined criteria. Patients may be newly diagnosed or have received prior cancer therapy

  • Patients must have had histologic verification of the malignancy
  • Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Patients must have a tumor showing the appropriate morphologic appearance, and either confirmed TFE3 nuclear protein expression by immunohistochemistry with appropriate positive and negative controls performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, or evidence of TFE3 or TFEb translocation by either fluorescence in situ hybridization (FISH) or reverse transcriptase- polymerase chain reaction (RT-PCR) performed at a CLIA-certified laboratory. For TFE3 immunohistochemistry, any nuclear positivity in the presence of appropriate positive and negative controls should be considered as evidence of TFE3 immunohistochemical expression. NOTE: If the institution is unable to perform these studies, unstained slides may be submitted to Dr. Elizabeth Perlman, who will perform TFE3 analysis at no charge. The slide will be returned to the referring institution for local evaluation, to be included in their institutional report

• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

• Patients must have a life expectancy of >= 8 weeks

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

  • Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
  • Immunotherapy: Must not have received within 4 weeks of entry onto this study
  • Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent
  • Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation

• Peripheral absolute neutrophil count (ANC) >= 1000/uL (performed within 7 days prior to enrollment)

• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)

• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)

• Urine protein: =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hours (h) urine sample (performed within 7 days prior to enrollment)

• For patients < 18 years of age: Serum creatinine =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 for patient with creatinine levels > 1.5 x institutional ULN, or a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment):

  • 1 to < 2 years - 0.6 mg/dL (male, female)
  • 2 to < 6 years - 0.8 mg/dL (male, female)
  • 6 to < 10 years - 1 mg/dL (male, female)
  • 10 to < 13 years - 1.2 mg/dL (male, female)
  • 13 to < 16 years - 1.5 mg/dL (male), 1.4 mg/dL (female)
  • >= 16 years - 1.7 mg/dL (male), 1.4 mg/dL (female)
  • Creatinine clearance should be calculated per institutional standard

• For patients >= 18 years of age: Serum creatinine =< 2 x ULN, or measured or calculated creatinine clearance or radioisotope GFR >= 40 mL/min/1.73 m^2 for patient with creatinine levels > 2 x institutional ULN (performed within 7 days prior to enrollment)

  • Creatinine clearance should be calculated per institutional standard

• Serum total bilirubin =< 1.5 x ULN for age, or direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 X ULN (performed within 7 days prior to enrollment)

• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN for age (performed within 7 days prior to enrollment)

• Albumin > 2.5 mg/dL (performed within 7 days prior to enrollment)

• Shortening fraction of >= 27% by echocardiogram, or

• Ejection fraction of >= 50% by radionuclide angiogram

• No history of myocardial infarction, severe or unstable angina, or peripheral vascular disease

• Corrected QT (QTc) =< 480 msec. Note: Patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)

• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN. However, if patient is receiving anticoagulant therapy, PT or partial thromboplastin time (PTT) should be within therapeutic range of intended use of anticoagulants

• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

• A baseline blood pressure (BP) =< the 95th percentile for age, height, and gender for patients < 18 years old, or =< 150 mmHg (systolic) and =< 90 mmHg (diastolic) for patients >= 18 years old

  • Note: 2 serial blood pressures should be taken at least 1 hour apart and averaged to determine baseline BP

• Patients are eligible if on stable doses (>= 7 days) of anti-hypertensive medications with a baseline BP meeting the criteria above

Exclusion Criteria

• Patients unable to swallow whole tablets

• Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible

• Prior Therapy

  • Patients who have received prior therapy with axitinib, nivolumab, or other PD1/PD-L1 targeted therapies

  • Patients who have received prior therapy with more than one anti VEGF based agent (antibody or tyrosine kinase inhibitor)

  • Patients with hypersensitivity to axitinib, nivolumab, or any of its excipients

  • Patients who previously received an allogeneic stem cell transplant (SCT) or solid organ transplant are not eligible

  • Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)

  • Patients who have received prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study enrollment or who have not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks prior to enrollment

  • Surgery: Patients who have had or who are planning to have the following invasive procedures are not eligible:

    • Major surgical procedure, laparoscopic procedure, open biopsy, core biopsy, fine needle aspirate, or significant traumatic injury within 7 days prior to enrollment. NOTE: External central lines must be placed at least 3 days prior to planned treatment initiation and subcutaneous ports must be placed at least 7 days prior to planned treatment initiation
    • Patients who are planning cytoreductive surgery within the first 12 weeks following therapy initiation
    • Patients who have a serious or non-healing wound or ulcer at the time of study enrollment are not eligible

  • Patients who have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment are not eligible

  • Patients who have received prior targeted small molecule therapy within 2 weeks of enrollment or have not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks prior to enrollment. NOTE: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study

• Pre-existing conditions, which may include:

  • Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
  • Patients with underlying immune deficiency, chronic infections including hepatitis, tuberculosis (TB), or autoimmune disease
  • Human immunodeficiency virus (HIV)-infected patients with the exception of patients on an effective anti-retroviral therapy with an undetectable viral load within 6 months prior to enrollment
  • Patients with underlying hematologic issues including congenital bleeding diathesis, known previous gastrointestinal (GI) bleeding requiring intervention within the past 6 months, history of hemoptysis within 42 days prior to study enrollment, active pulmonary emboli, or deep vein thromboses (DVT) that are not stable on anticoagulation regimen
  • Patients must not have had significant vascular disease (i.e. Moya-Moya, aortic aneurysm requiring surgical repair)
  • A known history of, or any evidence of active, non-infectious pneumonitis
  • Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study enrollment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study enrollment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
  • Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the investigator(s) to interfere or limit compliance with study requirements/treatment
  • Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

• Treatments and/or medications the patient is receiving or has received that would make her/him ineligible, including:

  • Concomitant (or receipt of) treatment with medications that may affect the metabolism of nivolumab and/or axitinib within 7 days prior to planned first dose of protocol therapy
  • A live vaccine within 30 days of planned first dose of protocol therapy. NOTE: Inactivated flu vaccines are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

• Pregnancy and breast feeding

  • Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of study drug
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 5 months after the last dose of study therapy

• Male patients of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy. Prior history of vasectomy does not replace requirement for contraceptive use

• Regulatory requirements

  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B (axitinib)	Axitinib	Patients receive axitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AS OF 1/23/2020 - PROSPECTIVE PATIENTS ARE RANDOMLY ASSIGNED TO ARMS A OR C)
Arm A (axitinib, nivolumab)	Axitinib	Patients receive axitinib PO BID on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Arm A (axitinib, nivolumab)	Nivolumab	Patients receive axitinib PO BID on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Arm C (nivolumab)	Nivolumab	Patients receive nivolumab IV over 30 minutes, or per institutional guidelines, on days 1 and 15 (if \< 18 years old) or on day 1 (if \>= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	Up to 1 year from study entry	The Kaplan-Meier method will be used to estimate 1-year PFS, defined as the time from randomization to disease progression or death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 1 year from study entry	The Kaplan-Meier method will be used to estimate 1-year OS, defined as the time from study entry until death.
Overall response rate (ORR)	Up to 1 year from study entry	The ORR will be defined as the proportion of patients that achieve a complete or partial response according to RECIST version 1.1 among patients who initiated protocol therapy and completed at least one subsequent imaging assessment.
Percentage of patients experiencing adverse events (AEs)	Up to 2 years from study entry	Percentage of patients experiencing grade 3+ non-hematologic and all grade 4-5 AEs occurring during protocol therapy or within 30 days of treatment will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Trial Locations

Locations (271)

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

CTCA at Western Regional Medical Center; 🇺🇸 Goodyear, Arizona, United States

Cancer Center at Saint Joseph's; 🇺🇸 Phoenix, Arizona, United States

CHI Saint Vincent Cancer Center Hot Springs; 🇺🇸 Hot Springs, Arkansas, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Kaiser Permanente-Anaheim; 🇺🇸 Anaheim, California, United States

Mission Hope Medical Oncology - Arroyo Grande; 🇺🇸 Arroyo Grande, California, United States

PCR Oncology; 🇺🇸 Arroyo Grande, California, United States

Kaiser Permanente-Bellflower; 🇺🇸 Bellflower, California, United States

Mercy Cancer Center - Carmichael; 🇺🇸 Carmichael, California, United States

Mercy San Juan Medical Center; 🇺🇸 Carmichael, California, United States

Kaiser Permanente Downey Medical Center; 🇺🇸 Downey, California, United States

Mercy Cancer Center - Elk Grove; 🇺🇸 Elk Grove, California, United States

Kaiser Permanente-Fontana; 🇺🇸 Fontana, California, United States

Kaiser Permanente Los Angeles Medical Center; 🇺🇸 Los Angeles, California, United States

Mattel Children's Hospital UCLA; 🇺🇸 Los Angeles, California, United States

Kaiser Permanente-Oakland; 🇺🇸 Oakland, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

Mercy Cancer Center - Rocklin; 🇺🇸 Rocklin, California, United States

Mercy Cancer Center - Sacramento; 🇺🇸 Sacramento, California, United States

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Kaiser Permanente-San Diego Mission; 🇺🇸 San Diego, California, United States

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

Mission Hope Medical Oncology - Santa Maria; 🇺🇸 Santa Maria, California, United States

Woodland Memorial Hospital; 🇺🇸 Woodland, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Penrose-Saint Francis Healthcare; 🇺🇸 Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose; 🇺🇸 Colorado Springs, Colorado, United States

Saint Francis Cancer Center; 🇺🇸 Colorado Springs, Colorado, United States

AdventHealth Porter; 🇺🇸 Denver, Colorado, United States

Presbyterian - Saint Lukes Medical Center - Health One; 🇺🇸 Denver, Colorado, United States

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center; 🇺🇸 Denver, Colorado, United States

Mercy Medical Center; 🇺🇸 Durango, Colorado, United States

Southwest Oncology PC; 🇺🇸 Durango, Colorado, United States

Mountain Blue Cancer Care Center; 🇺🇸 Golden, Colorado, United States

Rocky Mountain Cancer Centers-Lakewood; 🇺🇸 Lakewood, Colorado, United States

Saint Anthony Hospital; 🇺🇸 Lakewood, Colorado, United States

AdventHealth Littleton; 🇺🇸 Littleton, Colorado, United States

Longmont United Hospital; 🇺🇸 Longmont, Colorado, United States

Rocky Mountain Cancer Centers-Longmont; 🇺🇸 Longmont, Colorado, United States

AdventHealth Parker; 🇺🇸 Parker, Colorado, United States

Rocky Mountain Cancer Centers-Parker; 🇺🇸 Parker, Colorado, United States

Saint Mary Corwin Medical Center; 🇺🇸 Pueblo, Colorado, United States

Rocky Mountain Cancer Centers - Pueblo; 🇺🇸 Pueblo, Colorado, United States

Rocky Mountain Cancer Centers-Thornton; 🇺🇸 Thornton, Colorado, United States

Connecticut Children's Medical Center; 🇺🇸 Hartford, Connecticut, United States

Alfred I duPont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Broward Health Medical Center; 🇺🇸 Fort Lauderdale, Florida, United States

Golisano Children's Hospital of Southwest Florida; 🇺🇸 Fort Myers, Florida, United States

University of Florida Health Science Center - Gainesville; 🇺🇸 Gainesville, Florida, United States

Nemours Children's Clinic-Jacksonville; 🇺🇸 Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States

Nemours Children's Hospital; 🇺🇸 Orlando, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa; 🇺🇸 Tampa, Florida, United States

Saint Mary's Medical Center; 🇺🇸 West Palm Beach, Florida, United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital; 🇺🇸 Atlanta, Georgia, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

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

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

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

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

Saint Jude Midwest Affiliate; 🇺🇸 Peoria, Illinois, United States

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

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

Riley Hospital for Children; 🇺🇸 Indianapolis, Indiana, United States

Mercy Cancer Center-West Lakes; 🇺🇸 Clive, Iowa, United States

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

Alegent Health Mercy Hospital; 🇺🇸 Council Bluffs, Iowa, United States

Greater Regional Medical Center; 🇺🇸 Creston, Iowa, United States

Mercy Medical Center - Des Moines; 🇺🇸 Des Moines, Iowa, United States

UI Health Care Mission Cancer and Blood - Laurel Clinic; 🇺🇸 Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States

Desert West Surgery; 🇺🇸 Las Vegas, Nevada, United States

Mercy Medical Center-West Lakes; 🇺🇸 West Des Moines, Iowa, United States

Flaget Memorial Hospital; 🇺🇸 Bardstown, Kentucky, United States

Commonwealth Cancer Center-Corbin; 🇺🇸 Corbin, Kentucky, United States

Saint Joseph Hospital; 🇺🇸 Lexington, Kentucky, United States

Saint Joseph Radiation Oncology Resource Center; 🇺🇸 Lexington, Kentucky, United States

Saint Joseph Hospital East; 🇺🇸 Lexington, Kentucky, United States

Saint Joseph London; 🇺🇸 London, Kentucky, United States

Jewish Hospital; 🇺🇸 Louisville, Kentucky, United States

Norton Children's Hospital; 🇺🇸 Louisville, Kentucky, United States

Saints Mary and Elizabeth Hospital; 🇺🇸 Louisville, Kentucky, United States

UofL Health Medical Center Northeast; 🇺🇸 Louisville, Kentucky, United States

Saint Joseph Mount Sterling; 🇺🇸 Mount Sterling, Kentucky, United States

Jewish Hospital Medical Center South; 🇺🇸 Shepherdsville, Kentucky, United States

Ochsner Medical Center Jefferson; 🇺🇸 New Orleans, Louisiana, United States

Sinai Hospital of Baltimore; 🇺🇸 Baltimore, Maryland, United States

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

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

C S Mott Children's Hospital; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Health Saint John Hospital; 🇺🇸 Detroit, Michigan, United States

Huron Medical Center PC; 🇺🇸 Port Huron, Michigan, United States

Lake Huron Medical Center; 🇺🇸 Port Huron, Michigan, United States

Fairview Ridges Hospital; 🇺🇸 Burnsville, Minnesota, United States

Minnesota Oncology - Burnsville; 🇺🇸 Burnsville, Minnesota, United States

Cambridge Medical Center; 🇺🇸 Cambridge, Minnesota, United States

Mercy Hospital; 🇺🇸 Coon Rapids, Minnesota, United States

Fairview Southdale Hospital; 🇺🇸 Edina, Minnesota, United States

Unity Hospital; 🇺🇸 Fridley, Minnesota, United States

Fairview Clinics and Surgery Center Maple Grove; 🇺🇸 Maple Grove, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood; 🇺🇸 Maplewood, Minnesota, United States

Saint John's Hospital - Healtheast; 🇺🇸 Maplewood, Minnesota, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis; 🇺🇸 Minneapolis, Minnesota, United States

Abbott-Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

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

Health Partners Inc; 🇺🇸 Minneapolis, Minnesota, United States

Monticello Cancer Center; 🇺🇸 Monticello, Minnesota, United States

New Ulm Medical Center; 🇺🇸 New Ulm, Minnesota, United States

Fairview Northland Medical Center; 🇺🇸 Princeton, Minnesota, United States

North Memorial Medical Health Center; 🇺🇸 Robbinsdale, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park; 🇺🇸 Saint Louis Park, Minnesota, United States

Regions Hospital; 🇺🇸 Saint Paul, Minnesota, United States

United Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Saint Francis Regional Medical Center; 🇺🇸 Shakopee, Minnesota, United States

Lakeview Hospital; 🇺🇸 Stillwater, 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

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Children's Mercy Hospitals and Clinics; 🇺🇸 Kansas City, Missouri, United States

Cardinal Glennon Children's Medical Center; 🇺🇸 Saint Louis, Missouri, United States

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

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

Nebraska Cancer Specialists/Oncology Hematology West PC; 🇺🇸 Grand Island, Nebraska, United States

Fred and Pamela Buffett Cancer Center - Kearney; 🇺🇸 Kearney, Nebraska, United States

CHI Health Good Samaritan; 🇺🇸 Kearney, Nebraska, United States

Saint Elizabeth Regional Medical Center; 🇺🇸 Lincoln, Nebraska, United States

Alegent Health Immanuel Medical Center; 🇺🇸 Omaha, Nebraska, United States

Hematology and Oncology Consultants PC; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Bergan Mercy Medical Center; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Lakeside Hospital; 🇺🇸 Omaha, Nebraska, United States

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

Midlands Community Hospital; 🇺🇸 Papillion, Nebraska, 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

Comprehensive Cancer Centers of Nevada-Southeast Henderson; 🇺🇸 Henderson, Nevada, United States

GenesisCare USA - Henderson; 🇺🇸 Henderson, Nevada, United States

Las Vegas Urology - Green Valley; 🇺🇸 Henderson, Nevada, United States

Urology Specialists of Nevada - Green Valley; 🇺🇸 Henderson, Nevada, United States

OptumCare Cancer Care at Charleston; 🇺🇸 Las Vegas, Nevada, United States

University Medical Center of Southern Nevada; 🇺🇸 Las Vegas, Nevada, United States

Hope Cancer Care of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Cancer and Blood Specialists-Shadow; 🇺🇸 Las Vegas, Nevada, United States

Radiation Oncology Centers of Nevada Central; 🇺🇸 Las Vegas, Nevada, United States

Urology Specialists of Nevada - Central; 🇺🇸 Las Vegas, Nevada, United States

GenesisCare USA - Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway; 🇺🇸 Las Vegas, Nevada, United States

Sunrise Hospital and Medical Center; 🇺🇸 Las Vegas, Nevada, United States

HealthCare Partners Medical Group Oncology/Hematology-San Martin; 🇺🇸 Las Vegas, Nevada, United States

Las Vegas Urology - Sunset; 🇺🇸 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

Cancer Therapy and Integrative Medicine; 🇺🇸 Las Vegas, Nevada, United States

Ann M Wierman MD LTD; 🇺🇸 Las Vegas, Nevada, United States

Cancer and Blood Specialists-Tenaya; 🇺🇸 Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada - Northwest; 🇺🇸 Las Vegas, Nevada, United States

GenesisCare USA - Vegas Tenaya; 🇺🇸 Las Vegas, Nevada, United States

HealthCare Partners Medical Group Oncology/Hematology-Tenaya; 🇺🇸 Las Vegas, Nevada, United States

OptumCare Cancer Care at MountainView; 🇺🇸 Las Vegas, Nevada, United States

Urology Specialists of Nevada - Northwest; 🇺🇸 Las Vegas, Nevada, United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation; 🇺🇸 Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada - Town Center; 🇺🇸 Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada-Summerlin; 🇺🇸 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; 🇺🇸 Las Vegas, Nevada, United States

GenesisCare USA - Fort Apache; 🇺🇸 Las Vegas, Nevada, United States

OptumCare Cancer Care at Fort Apache; 🇺🇸 Las Vegas, Nevada, United States

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills; 🇺🇸 Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada - Central Valley; 🇺🇸 Las Vegas, Nevada, United States

University Cancer Center; 🇺🇸 Las Vegas, Nevada, United States

Hope Cancer Care of Nevada-Pahrump; 🇺🇸 Pahrump, Nevada, United States

Renown Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Saint Mary's Regional Medical Center; 🇺🇸 Reno, Nevada, United States

Radiation Oncology Associates; 🇺🇸 Reno, Nevada, United States

Cancer Care Specialists - Reno; 🇺🇸 Reno, Nevada, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

Montefiore Medical Center - Moses Campus; 🇺🇸 Bronx, New York, United States

Maimonides Medical Center; 🇺🇸 Brooklyn, New York, United States

The Steven and Alexandra Cohen Children's Medical Center of New York; 🇺🇸 New Hyde Park, New York, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

State University of New York Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Mission Hospital; 🇺🇸 Asheville, North Carolina, United States

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

Carolinas Medical Center/Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Children's Hospital Medical Center of Akron; 🇺🇸 Akron, Ohio, United States

Good Samaritan Hospital - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Bethesda North Hospital; 🇺🇸 Cincinnati, Ohio, United States

TriHealth Cancer Institute-Westside; 🇺🇸 Cincinnati, Ohio, United States

TriHealth Cancer Institute-Anderson; 🇺🇸 Cincinnati, Ohio, United States

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

Rainbow Babies and Childrens Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Dayton Children's Hospital; 🇺🇸 Dayton, Ohio, United States

ProMedica Flower Hospital; 🇺🇸 Sylvania, Ohio, United States

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital; 🇺🇸 Toledo, Ohio, United States

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

Cancer Treatment Centers of America; 🇺🇸 Tulsa, Oklahoma, United States

Legacy Emanuel Children's Hospital; 🇺🇸 Portland, Oregon, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Prisma Health Cancer Institute - Spartanburg; 🇺🇸 Boiling Springs, South Carolina, United States

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

Prisma Health Cancer Institute - Laurens; 🇺🇸 Clinton, South Carolina, United States

Prisma Health Cancer Institute - Easley; 🇺🇸 Easley, South Carolina, United States

Prisma Health Cancer Institute - Butternut; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Faris; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Eastside; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Greer; 🇺🇸 Greer, South Carolina, United States

Prisma Health Cancer Institute - Seneca; 🇺🇸 Seneca, South Carolina, United States

Memorial Hospital; 🇺🇸 Chattanooga, Tennessee, United States

Pulmonary Medicine Center of Chattanooga-Hixson; 🇺🇸 Hixson, Tennessee, United States

East Tennessee Childrens Hospital; 🇺🇸 Knoxville, Tennessee, United States

Saint Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

The Children's Hospital at TriStar Centennial; 🇺🇸 Nashville, Tennessee, United States

Memorial GYN Plus; 🇺🇸 Ooltewah, Tennessee, United States

Dell Children's Medical Center of Central Texas; 🇺🇸 Austin, Texas, United States

Saint Joseph Regional Cancer Center; 🇺🇸 Bryan, Texas, United States

El Paso Children's Hospital; 🇺🇸 El Paso, Texas, United States

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Children's Hospital of San Antonio; 🇺🇸 San Antonio, Texas, United States

Methodist Children's Hospital of South Texas; 🇺🇸 San Antonio, Texas, United States

University Hospital; 🇺🇸 San Antonio, Texas, United States

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

Children's Hospital of The King's Daughters; 🇺🇸 Norfolk, Virginia, United States

Overlake Medical Center; 🇺🇸 Bellevue, Washington, United States

Highline Medical Center-Main Campus; 🇺🇸 Burien, Washington, United States

Saint Elizabeth Hospital; 🇺🇸 Enumclaw, Washington, United States

Saint Francis Hospital; 🇺🇸 Federal Way, Washington, United States

Saint Clare Hospital; 🇺🇸 Lakewood, Washington, United States

Harrison HealthPartners Hematology and Oncology-Poulsbo; 🇺🇸 Poulsbo, Washington, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Saint Michael Cancer Center; 🇺🇸 Silverdale, Washington, United States

Providence Sacred Heart Medical Center and Children's Hospital; 🇺🇸 Spokane, Washington, United States

Franciscan Research Center-Northwest Medical Plaza; 🇺🇸 Tacoma, Washington, United States

Mary Bridge Children's Hospital and Health Center; 🇺🇸 Tacoma, Washington, United States

Northwest Medical Specialties PLLC; 🇺🇸 Tacoma, Washington, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital; 🇺🇸 Yakima, Washington, United States

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

Saint Vincent Hospital Cancer Center Green Bay; 🇺🇸 Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's; 🇺🇸 Green Bay, Wisconsin, United States

Holy Family Memorial Hospital; 🇺🇸 Manitowoc, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Marinette; 🇺🇸 Marinette, Wisconsin, United States

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

Children's Hospital of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Cancer Center of Western Wisconsin; 🇺🇸 New Richmond, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Oconto Falls; 🇺🇸 Oconto Falls, Wisconsin, United States

HSHS Saint Nicholas Hospital; 🇺🇸 Sheboygan, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay; 🇺🇸 Sturgeon Bay, Wisconsin, United States

HIMA San Pablo Oncologic Hospital; 🇵🇷 Caguas, Puerto Rico