A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
- Conditions
- Acral Lentiginous MelanomaMetastatic Cutaneous MelanomaMetastatic MelanomaMetastatic Mucosal MelanomaClinical Stage IV Cutaneous Melanoma AJCC v8Metastatic Malignant Neoplasm in the BrainPathologic Stage IV Cutaneous Melanoma AJCC v8
- Interventions
- Registration Number
- NCT04511013
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. This trial aims to find out which approach is more effective in shrinking and controlling brain metastases from melanoma.
- Detailed Description
PRIMARY OBJECTIVE:
I. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between participants randomized to the triplet combination of encorafenib + binimetinib + nivolumab versus the doublet combination of ipilimumab + nivolumab among participants with BRAF-V600 mutant melanoma that has metastasized to the brain.
SECONDARY OBJECTIVES:
I. To estimate the overall survival (OS) of participants in each treatment arm. II. To estimate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial responses) per RECIST 1.1 in each treatment arm.
III. To estimate the intracranial response rate (ICRR), defined as confirmed and unconfirmed complete and partial response per modified RECIST for brain metastases (mRECIST).
IV. To evaluate the duration of response, per RECIST 1.1 and the duration of ICRR per mRECIST, and per Response Assessment in Neuro-Oncology (RANO)-Brain Metastases (BM) (and immunotherapy \[i\]RANO) in each treatment arm.
V. To evaluate the toxicity profile of each treatment arm. VI. To evaluate current and emerging radiographic response criteria (modified RECIST 1.1, modified RANO-BM and iRANO) by a retrospective blinded independent centralized review (BICR) of banked images.
BANKING OBJECTIVE:
I. To bank tumor tissue, cerebral spinal fluid (CSF), stool and blood samples for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, binimetinib PO twice daily (BID) on days 1-28, and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years, and then annually until 3 years after randomization.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 112
- Participants must have histologically and pathologically confirmed melanoma that has metastasized to the brain
- Any primary (cutaneous, acral/mucosal, etc) or unknown origin are permitted, except that participants with uveal primary are not eligible
- Participants must have BRAF-V600 mutant melanoma documented by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
- All participants must have an magnetic resonance imaging (MRI) of the brain within 28 days prior to registration and must have central nervous system metastases with at least one measurable brain metastasis >= 0.5 cm in size (per modified RECIST 1.1) that has not been irradiated, or progressed (in the opinion of the treating physician) after prior radiation therapy. Participating sites MUST use MRI slice thickness of =< 1.5 mm and are recommended to adhere to the 'minimum' Brain Tumor Imaging Protocol for Clinical Trials in Brain Metastases (BTIP-BM) compliant MRI acquisition protocol. Computed tomography (CT) of the head cannot substitute for brain MRI. (NOTE: All central nervous system [CNS] disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form [RECIST 1.1] using RECIST 1.1.)
- Participants may have measurable or non-measurable extracranial disease. All measurable disease must be assessed within 28 days prior to randomization; all non-measurable disease must be assessed within 42 days prior to randomization. Please note, while any extracranial disease will also be assessed and followed, participants are NOT required to have extracranial disease for randomization. NOTE: All disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). CNS disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form (RECIST 1.1) using RECIST 1.1
- Participants may have leptomeningeal disease
- Participants may be receiving corticosteroids for brain metastases at a dose of up to 8 mg of dexamethasone per day. The dose must not have exceeded 8 mg per day for at least 7 days prior to randomization
- Participants must have Zubrod performance status =< 2
- Participants must have complete history and physical examination within 28 days prior to randomization
- Participants must be able to swallow and retain pills
- Hemoglobin >= 8.0 g/dL (within 28 days prior to randomization)
- Absolute neutrophil count >= 1,500/mcL (within 28 days prior to randomization)
- Platelets >= 75,000/mcL (within 28 days prior to randomization)
- Total bilirubin =< 1.5 institutional upper limit of normal (ULN) (within 28 days prior to randomization)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN (in participants with liver metastases =< 5 x ULN) (within 28 days prior to randomization)
- Creatinine =< 2.0 institutional ULN (within 28 days prior to randomization)
- Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
- Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization
- Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization
- Participants must agree to participate in image banking. Images must be submitted via the Triad System
- Participants must be offered the opportunity to participate in specimen and blood collections
- 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
- As a part of the 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
- Participants must not have received prior systemic therapy for metastatic disease. Prior systemic therapy received only in the neoadjuvant and/or adjuvant setting (e.g., BRAF/MEK inhibitor therapy, anti-PD-1 therapy or anti-CTLA4 therapy, alfa-interferon, etc.) is permitted. If patients received prior neoadjuvant/adjuvant therapy, they must have had eventual disease relapse prior to randomization
- Participants must not have had prior radiation therapy within 7 days prior to randomization
- Participants must not be planning to require any additional form of systemic anti-tumor therapy for melanoma while on protocol treatment
- Participants must not be planning to use hormonal contraceptives
- Participants must not have a serious active infection requiring systemic therapy at time of randomization in the opinion of the treating physician
- Participants must not have active autoimmune disease that has required treatment in the past 6 months with use of biologic disease modifying agents (.e.g. infliximab, adalimumab). Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =< 10 mg prednisone daily or equivalent (to treat auto-immune disease), or on replacement therapy (e.g., thyroxine, insulin) are eligible if deemed in the best interest of the patient by treating physician
- Participants must not have had grade 3 or 4 immune-related adverse events on ipilimumab or nivolumab that required more than 12 weeks of immune suppression with corticosteroids
- Participants must not have had adverse events related to encorafenib and/or binimetinib specifically, that required discontinuation of one or both drugs. (Please note this does not apply to other BRAF/MEK inhibitor drugs.)
- Participants must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective method of contraception. (NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.) A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (encorafenib, binimetinib, nivolumab) Nivolumab Patients receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (nivolumab, ipilimumab) Nivolumab Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (nivolumab, ipilimumab) Ipilimumab Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (encorafenib, binimetinib, nivolumab) Binimetinib Patients receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm I (encorafenib, binimetinib, nivolumab) Encorafenib Patients receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free survival From date of registration to date of first documentation of progression, or symptomatic deterioration, or death due to any cause, assessed up to 3 years after randomization Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Secondary Outcome Measures
Name Time Method Duration of response Up to 3 years after randomization Overall survival (OS) From date of registration to date of death due to any cause, assessed up to 3 years after randomization Will be assessed by Immunotherapy Response Assessment Criteria for Intracranial Metastases (RANO-BM). Will construct Kaplan-Meier plots and estimate the median OS and construct 95% Brookmeyer-Crowley Confidence intervals.
Intracranial response rate (ICRR) Up to 3 years after randomization The ICRR is defined as the best response when applying modified (m)RECIST criteria. Will compare intracranial response based on assessments per mRECIST, RANO-BM and immunotherapy (i)RANO criteria based on a review of the banked images. For each of these methods, the best response to treatment will be summarized by treatment arm, the percent agreement between each pair of methods will be reported along with a 95% confidence interval, and a p-value based on a two-sided McNemar's test will be calculated.
Objective response rate Up to 3 years after randomization Will be assessed by RECIST 1.1.
Trial Locations
- Locations (331)
Columbus Oncology and Hematology Associates Inc
🇺🇸Columbus, Ohio, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
Mount Carmel Health Center West
🇺🇸Columbus, Ohio, United States
Swedish Medical Center-Cherry Hill
🇺🇸Seattle, Washington, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Methodist West Hospital
🇺🇸West Des Moines, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
Saint Anthony Regional Hospital
🇺🇸Carroll, Iowa, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Lakeland Medical Center Saint Joseph
🇺🇸Saint Joseph, Michigan, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Mercy Health - Paducah Medical Oncology and Hematology
🇺🇸Paducah, Kentucky, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Lakeland Hospital Niles
🇺🇸Niles, Michigan, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
Ascension Borgess Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Trinity Regional Medical Center
🇺🇸Fort Dodge, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Spectrum Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Orion Cancer Care
🇺🇸Findlay, Ohio, United States
OhioHealth Marion General Hospital
🇺🇸Marion, Ohio, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Knox Community Hospital
🇺🇸Mount Vernon, Ohio, United States
Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
UH Seidman Cancer Center at Firelands Regional Medical Center
🇺🇸Sandusky, Ohio, United States
Southern Ohio Medical Center
🇺🇸Portsmouth, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Providence Regional Cancer System-Lacey
🇺🇸Lacey, Washington, United States
Swedish Medical Center-Ballard Campus
🇺🇸Seattle, Washington, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Swedish Cancer Institute-Issaquah
🇺🇸Issaquah, Washington, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Providence Regional Cancer System-Shelton
🇺🇸Shelton, Washington, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Cheyenne Regional Medical Center-West
🇺🇸Cheyenne, Wyoming, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Billings Clinic-Cody
🇺🇸Cody, Wyoming, United States
Rocky Mountain Cancer Centers-Rose
🇺🇸Denver, Colorado, United States
Western Surgical Care
🇺🇸Denver, Colorado, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
Fairview Northland Medical Center
🇺🇸Princeton, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Southwest Illinois Health Services LLP
🇺🇸Swansea, Illinois, United States
Broadlawns Medical Center
🇺🇸Des Moines, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
Rocky Mountain Cancer Centers-Aurora
🇺🇸Aurora, Colorado, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center-International Plaza
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Providence Saint Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
University of Michigan - Brighton Center for Specialty Care
🇺🇸Brighton, Michigan, United States
Cambridge Medical Center
🇺🇸Cambridge, Minnesota, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Mobile Infirmary Medical Center
🇺🇸Mobile, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Thomas Hospital
🇺🇸Fairhope, Alabama, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
Fairbanks Memorial Hospital
🇺🇸Fairbanks, Alaska, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
Bay Area Breast Surgeons Inc
🇺🇸Emeryville, California, United States
Epic Care-Dublin
🇺🇸Dublin, California, United States
UCLA / Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Epic Care Partners in Cancer Care
🇺🇸Emeryville, California, United States
Contra Costa Regional Medical Center
🇺🇸Martinez, California, United States
Providence Queen of The Valley
🇺🇸Napa, California, United States
Alta Bates Summit Medical Center - Summit Campus
🇺🇸Oakland, California, United States
Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Epic Care Cyberknife Center
🇺🇸Walnut Creek, California, United States
Providence Medical Foundation - Santa Rosa
🇺🇸Santa Rosa, California, United States
Providence Santa Rosa Memorial Hospital
🇺🇸Santa Rosa, California, United States
Boulder Community Foothills Hospital
🇺🇸Boulder, Colorado, United States
Rocky Mountain Cancer Centers-Boulder
🇺🇸Boulder, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers-Midtown
🇺🇸Denver, Colorado, United States
The Women's Imaging Center
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers - Centennial
🇺🇸Centennial, Colorado, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
Mountain Blue Cancer Care Center - Swedish
🇺🇸Englewood, Colorado, United States
The Melanoma and Skin Cancer Institute
🇺🇸Englewood, Colorado, United States
Rocky Mountain Cancer Centers - Swedish
🇺🇸Englewood, Colorado, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Rocky Mountain Cancer Centers-Littleton
🇺🇸Littleton, Colorado, United States
Rocky Mountain Cancer Centers-Sky Ridge
🇺🇸Lone Tree, Colorado, United States
Rocky Mountain Cancer Centers-Lakewood
🇺🇸Lakewood, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
Rocky Mountain Cancer Centers-Thornton
🇺🇸Thornton, Colorado, United States
UM Sylvester Comprehensive Cancer Center at Aventura
🇺🇸Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
🇺🇸Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
🇺🇸Plantation, Florida, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur d'Alene, Idaho, United States
Walter Knox Memorial Hospital
🇺🇸Emmett, Idaho, United States
Idaho Urologic Institute-Meridian
🇺🇸Meridian, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
Kootenai Cancer Clinic
🇺🇸Sandpoint, Idaho, United States
Saint Anthony's Health
🇺🇸Alton, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
SIH Cancer Institute
🇺🇸Carterville, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Saint Mary's Hospital
🇺🇸Centralia, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Illinois CancerCare-Dixon
🇺🇸Dixon, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Reid Health
🇺🇸Richmond, Indiana, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Capital Region Southwest Campus
🇺🇸Jefferson City, Missouri, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
Missouri Baptist Outpatient Center-Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Community Hospital of Anaconda
🇺🇸Anaconda, Montana, United States
Bozeman Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Cancer Partners of Nebraska - Pine Lake
🇺🇸Lincoln, Nebraska, United States
Community Medical Hospital
🇺🇸Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Southeast Nebraska Cancer Center - 68th Street Place
🇺🇸Lincoln, Nebraska, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Wake Forest University at Clemmons
🇺🇸Clemmons, North Carolina, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸Clinton, North Carolina, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸Goldsboro, North Carolina, United States
Wake Forest Baptist Health - Hematology Oncology - Statesville
🇺🇸Statesville, North Carolina, United States
Wake Forest Baptist Health - Wilkes Medical Center
🇺🇸Wilkesboro, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸Jacksonville, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Beachwood, Ohio, United States
Strecker Cancer Center-Belpre
🇺🇸Belpre, Ohio, United States
Indu and Raj Soin Medical Center
🇺🇸Beavercreek, Ohio, United States
Saint Elizabeth Boardman Hospital
🇺🇸Boardman, Ohio, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
Dayton Physicians LLC-Miami Valley South
🇺🇸Centerville, Ohio, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸Cincinnati, Ohio, United States
Geauga Hospital
🇺🇸Chardon, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Mount Carmel East Hospital
🇺🇸Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
The Mark H Zangmeister Center
🇺🇸Columbus, Ohio, United States
Doctors Hospital
🇺🇸Columbus, Ohio, United States
Dayton Physician LLC-Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
Columbus Oncology and Hematology Associates
🇺🇸Dublin, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Delaware Health Center-Grady Cancer Center
🇺🇸Delaware, Ohio, United States
Dublin Methodist Hospital
🇺🇸Dublin, Ohio, United States
Armes Family Cancer Center
🇺🇸Findlay, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸Franklin, Ohio, United States
Central Ohio Breast and Endocrine Surgery
🇺🇸Gahanna, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Mount Carmel Grove City Hospital
🇺🇸Grove City, Ohio, United States
Dayton Physicians LLC-Wayne
🇺🇸Greenville, Ohio, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Zangmeister Center Grove City
🇺🇸Grove City, Ohio, United States
Saint Rita's Medical Center
🇺🇸Lima, Ohio, United States
OhioHealth Mansfield Hospital
🇺🇸Mansfield, Ohio, United States
UH Seidman Cancer Center at Southwest General Hospital
🇺🇸Middleburg Heights, Ohio, United States
Mount Carmel New Albany Surgical Hospital
🇺🇸New Albany, Ohio, United States
Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Mercy Health Perrysburg Cancer Center
🇺🇸Perrysburg, Ohio, United States
Newark Radiation Oncology
🇺🇸Newark, Ohio, United States
University Hospitals Parma Medical Center
🇺🇸Parma, Ohio, United States
Springfield Regional Cancer Center
🇺🇸Springfield, Ohio, United States
University Hospitals Portage Medical Center
🇺🇸Ravenna, Ohio, United States
Mercy Health - Saint Anne Hospital
🇺🇸Toledo, Ohio, United States
Springfield Regional Medical Center
🇺🇸Springfield, Ohio, United States
Saint Vincent Mercy Medical Center
🇺🇸Toledo, Ohio, United States
Dayton Physicians LLC - Troy
🇺🇸Troy, Ohio, United States
University Hospitals Sharon Health Center
🇺🇸Wadsworth, Ohio, United States
Saint Joseph Warren Hospital
🇺🇸Warren, Ohio, United States
Saint Ann's Hospital
🇺🇸Westerville, Ohio, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
UH Seidman Cancer Center at Saint John Medical Center
🇺🇸Westlake, Ohio, United States
Saint Elizabeth Youngstown Hospital
🇺🇸Youngstown, Ohio, United States
Saint Alphonsus Medical Center-Baker City
🇺🇸Baker City, Oregon, United States
Saint Charles Health System
🇺🇸Bend, Oregon, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
Bay Area Hospital
🇺🇸Coos Bay, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Saint Alphonsus Medical Center-Ontario
🇺🇸Ontario, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Saint Charles Health System-Redmond
🇺🇸Redmond, Oregon, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Providence Regional Cancer System-Aberdeen
🇺🇸Aberdeen, Washington, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Providence Regional Cancer System-Centralia
🇺🇸Centralia, Washington, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Pacific Gynecology Specialists
🇺🇸Seattle, Washington, United States
Jefferson Healthcare
🇺🇸Port Townsend, Washington, United States
PeaceHealth United General Medical Center
🇺🇸Sedro-Woolley, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
Providence Regional Cancer System-Yelm
🇺🇸Yelm, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Aspirus Medford Hospital
🇺🇸Medford, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Ascension Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
🇺🇸Savannah, Georgia, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
Genesis Healthcare System Cancer Care Center
🇺🇸Zanesville, Ohio, United States
Providence Regional Cancer Partnership
🇺🇸Everett, Washington, United States
PeaceHealth Saint John Medical Center
🇺🇸Longview, Washington, United States