Bevacizumab With or Without Anti-Endoglin Monoclonal Antibody TRC105 in Treating Patients With Recurrent Glioblastoma Multiforme

Phase 1

Completed

Conditions: Adult Giant Cell Glioblastoma
Recurrent Adult Brain Neoplasm
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Gliosarcoma
Adult Mixed Glioma
Adult Glioblastoma

Interventions: Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105
Biological: Bevacizumab
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other: Quality-of-Life Assessment

Registration Number: NCT01648348

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This partially randomized phase I/II trial studies the side effects and the best dose of anti-endoglin monoclonal antibody TRC105 when given together with bevacizumab and to see how well they work in treating patients with glioblastoma multiforme that has come back. Monoclonal antibodies, such as anti-endoglin monoclonal antibody TRC105 and bevacizumab, may find tumor cells and help kill them. Giving anti-endoglin monoclonal antibody TRC105 together with bevacizumab may be an effective treatment for glioblastoma multiforme.

Detailed Description: PRIMARY OBJECTIVES:

I. To establish a maximum tolerated dose (MTD) of TRC105 (anti-endoglin monoclonal antibody TRC105) combined with bevacizumab in this patient population. (Phase I) II. To assess the safety and adverse events of TRC105 in combination with bevacizumab in this patient population. (Phase II) III. To determine the efficacy of TRC105 in combination with bevacizumab in recurrent glioblastoma as measured by progression-free survival and compare it with the efficacy of bevacizumab alone in this patient population. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the proportion of patients, who are progression free at 6 months, treated with TRC105 in combination with bevacizumab as compared to bevacizumab alone. (Phase II) II. To assess the overall survival of patients treated with TRC105 in combination with bevacizumab compared to bevacizumab alone. (Phase II) III. To compare the impact of the treatment on the patients quality of life (QOL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C15-Palliative Care (PAL) and QLQ-brain neoplasm (BN)20 Patient Questionnaires. (Phase II) IV. To estimate patient recommendations for study participation to others using the Was It Worth It (WIWI) Questionnaire. (Phase II)

TERTIARY OBJECTIVES:

I. To evaluate the pharmacokinetics of TRC105. (Phase I) II. To evaluate the immunogenicity of TRC105. (Phase I) III. To determine the relationship between tumor biomarkers, circulating biomarkers of vascular response and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) single-nucleotide polymorphisms (SNPs) in predicting efficacy and/or toxicity of treatment. (Phase II) IV. To assess the utility of magnetic resonance imaging (MRI) imaging including apparent diffusion coefficient (ADC) as a predictor of response and survival. (Phase II) V. To assess the utility of dynamic contrast enhanced (DCE) MRI as a predictor of response to bevacizumab with or without TRC105. (Phase II)

OUTLINE: This is a phase I dose-escalation study of anti-endoglin monoclonal antibody TRC105, followed by a randomized phase II study.

Phase I (closed to accrual 1/14/14): Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Phase II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 116

Inclusion Criteria

Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review (Phase I)
Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review; note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible; glioblastoma (GBM) with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q co-deleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q co-deletion status (Phase II)
Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
Measurable or evaluable disease by gadolinium MRI or contrast CT scan; note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
Absolute neutrophil count (ANC) >= 1,500/mm^3
Platelet count >= 100,000/mm^3
White blood cells (WBC) >= 3,000/mL
Hemoglobin >= 10.0 g/dL; note: this level may be reached by transfusion
Total bilirubin =< institutional upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN
Creatinine =< ULN
Life expectancy >= 12 weeks
Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
Urine protein creatinine (UPC) ratio < 1; note: urine protein must be screened by urine analysis for UPC ratio; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration
Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to registration
Calculated glomerular filtration rate (GFR) must be >= 60 ml/min; GFR will be calculated as needed per institutional guidelines
Any number of prior chemotherapy regimens for recurrent disease (Phase I); =< 1 chemotherapy or other non-antiangiogenic regimen for recurrent disease (Phase II)
Last dose of bevacizumab >= 2 weeks prior to registration (Phase I); note: for the phase II study only, prior exposure to bevacizumab is not allowed
Surgery >= 4 weeks prior to registration
Completion of radiation therapy >= 12 weeks prior to registration and prior chemotherapy >= 4 weeks prior to registration (>= 6 weeks from nitrosourea-containing regimens)
Small molecular cell cycle inhibitors >= 2 weeks from registration
Ability to provide informed written consent
Ability to complete questionnaire(s) by themselves or with assistance
Willing to return to enrolling institution for follow-up
Willing to discontinue use of medications that inhibit platelet function >= 10 days prior to registration; aspirin at doses greater than 325 mg/day must be discontinued >= 10 days prior to registration and avoided through the study; note: nonsteroidal anti-inflammatory drug (NSAID) medications are recommended in place of aspirin; if NSAIDs or aspirin are used, histamine (H)-2 blockers and proton pump inhibitor (PPI) medications are recommended
Willing to provide mandatory blood and tissue samples for correlative research purposes (Phase I and II)

Exclusion Criteria

Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for at least 6 months after treatment has ended
Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)
Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)
Prior hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (Phase I and II)
Prior hypersensitivity to triptan derivatives (Phase I and II)
Other active malignancy =< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
Uncontrolled infection
Immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive and currently receiving combination antiretroviral therapy; patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
History of hypertensive crisis or hypertensive encephalopathy
Clinically significant cardiovascular disease defined as follows:
- Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive therapy)
- History of cerebrovascular accident (CVA) within 6 months
- Myocardial infarction or unstable angina within 6 months
- New York Heart Association classification II, III, or IV cardiovascular disease
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)
- Clinically significant peripheral vascular disease
Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., hereditary hemorrhagic telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed
Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
Prior treatment with TRC105
Serious or non-healing wound, active ulcer, or untreated bone fracture
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration
History of invasive procedures defined as follows:
- Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to registration
- Anticipation of need for major surgical procedures during the study
- Core biopsy =< 7 days prior to registration
History of significant vascular disease (i.e., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to registration

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (bevacizumab and TRC105)	Anti-Endoglin Chimeric Monoclonal Antibody TRC105	Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm I (bevacizumab and TRC105)	Bevacizumab	Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm I (bevacizumab and TRC105)	Laboratory Biomarker Analysis	Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm I (bevacizumab and TRC105)	Pharmacological Study	Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm I (bevacizumab and TRC105)	Quality-of-Life Assessment	Patients receive bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II (bevacizumab)	Quality-of-Life Assessment	Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II (bevacizumab)	Pharmacological Study	Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II (bevacizumab)	Bevacizumab	Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II (bevacizumab)	Laboratory Biomarker Analysis	Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities	28 days	MTD for this study will be defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of DLT's will be reported here.
Progression-free Survival (PFS) (Phase II)	The time from study randomization to documentation of disease progression, assessed up to 2 years	Progression Free Survival time is defined as the time from study randomization to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy or date last known to be alive, whichever is later. Patients who are still alive and have not progressed will be censored for progression at the time of the last tumor assessment. The time-to-progression distribution will be estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (Phase II)	The time from start of study therapy to death due to any cause, assessed up to 2 years	Survival time is defined to be the length of time from start of study therapy to death due to any cause. All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable for estimation of the survival distribution. The distribution of overall survival for both groups of the study will be estimated using the Kaplan-Meier method, and be compared using log-rank tests.
Quality of Life (QOL) as Assessed by the EORTC QLQ-C15-PAL Questionnaire [Item 15: Global Health Status/Quality of Life] (Phase II)	Baseline and 4 weeks	Quality of Life (QOL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire, as measured by the change from baseline to the end of cycle 2 (4 weeks) in the EORTC QLQ-C15-PAL item 15, Global health status/quality of life, score. The assessment was scored using EORTC's scoring algorithms. The score range is from 0-100 (0 corresponding to worst outcome; 100 corresponding to best outcome). Range of the change in scores from baseline to cycle 2 (4 weeks) is (-100,100). The mean change in score and 95% confidence interval of the change from baseline to the end of cycle 2 (4 weeks) are reported below.
Overall Toxicity Rate for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment (Phase II)	Up to 2 years	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment will be compared using a Fisher's Exact test between the 2 treatment groups.
Progression Free Survival at 6 Months (PFS6) (Phase II) as Measured by the Percentage of Participants With Progression Free Survival at 6 Months	The time from study randomization to documentation of disease progression, assessed at 6 months	PFS6 is defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause (whichever comes first). The medians and confidence intervals given are the Kaplan-Meier estimates.
QOL Assessed by WIWI Questionnaire (Phase II)	Up to 4 weeks	Quality of life (QOL) assessed by Was it worth it? (WIWI) questionnaire, as measured by the percentage of patients answering yes to the question "Was it worthwhile for you to participate in this research study?"
QOL Assessed by EORTC-QLQ-BN20 Patient Questionnaire [Items 1-20] (Phase II)	Baseline and 4 weeks	QOL assessed by EORTC-QLQ-BN20 Patient Questionnaire (Brain cancer module), as measured by the change from baseline to the end of cycle 2 (4 weeks) in the EORTC QLQ-BN20 Items 1-20 are used to score the following 11 symptom scales: Future uncertainty (Items 1-3,5), Visual disorder (Items 6-8), Motor dysfunction (Items 10,15, 19), Communication deficit (Items 11-13), Headaches (Item 4), Seizures (Item 9), Drowsiness (Item 14), Itchy Skin (Item 17), Hair Loss (Item 16), Weakness of legs (Item 18), and Bladder control (Item 20). The assessment was scored using EORTC's scoring algorithms. The score range for each of the 11 symptom scales is from 0-100 (0 corresponding to not severe;100 corresponding to most severe). Range of changes in scores from baseline to cycle 2 (4 weeks) is (-100,100). The mean change in score and 95% confidence interval of each symptom scale are reported below.

Trial Locations

Locations (307): Altru Cancer Center
🇺🇸
Grand Forks, North Dakota, United States
Greenville Health System Cancer Institute-Easley
🇺🇸
Easley, South Carolina, United States
Kootenai Medical Center
🇺🇸
Coeur d'Alene, Idaho, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Regional Hematology and Oncology PA
🇺🇸
Newark, Delaware, United States
Kootenai Cancer Center
🇺🇸
Post Falls, Idaho, United States
Beebe Health Campus
🇺🇸
Rehoboth Beach, Delaware, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
New Hampshire Oncology Hematology PA-Concord
🇺🇸
Concord, New Hampshire, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
New Hampshire Oncology Hematology PA-Hooksett
🇺🇸
Hooksett, New Hampshire, United States
MD Anderson Cancer Center at Cooper-Voorhees
🇺🇸
Voorhees, New Jersey, United States
LRGHealthcare-Lakes Region General Hospital
🇺🇸
Laconia, New Hampshire, United States
Greenville Health System Cancer Institute-Eastside
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Greenville, South Carolina, United States
Greenwich Hospital
🇺🇸
Greenwich, Connecticut, United States
Saint Jude Medical Center
🇺🇸
Fullerton, California, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸
Hartford, Connecticut, United States
Medical Oncology Hematology Consultants PA
🇺🇸
Newark, Delaware, United States
Mount Sinai Medical Center
🇺🇸
Miami Beach, Florida, United States
Trinity Medical Center
🇺🇸
Moline, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
🇺🇸
Highland Park, Illinois, United States
Saint Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Nanticoke Memorial Hospital
🇺🇸
Seaford, Delaware, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Christiana Care Health System-Wilmington Hospital
🇺🇸
Wilmington, Delaware, United States
Memorial Hospital of Carbondale
🇺🇸
Carbondale, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸
Pekin, Illinois, United States
Memorial Regional Cancer Center Day Road
🇺🇸
Mishawaka, Indiana, United States
Cancer Care Specialists of Illinois-Swansea
🇺🇸
Swansea, Illinois, United States
Illinois CancerCare-Canton
🇺🇸
Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸
Carthage, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
🇺🇸
Peoria, Illinois, United States
Crossroads Cancer Center
🇺🇸
Effingham, Illinois, United States
Kootenai Cancer Clinic
🇺🇸
Sandpoint, Idaho, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸
Evanston, Illinois, United States
Hematology Oncology Associates of Illinois - Skokie
🇺🇸
Skokie, Illinois, United States
Cancer Care Center of Decatur
🇺🇸
Decatur, Illinois, United States
Central Illinois Hematology Oncology Center
🇺🇸
Springfield, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸
Peoria, Illinois, United States
NorthShore Hematology Oncology-Libertyville
🇺🇸
Libertyville, Illinois, United States
Valley Radiation Oncology
🇺🇸
Peru, Illinois, United States
Michiana Hematology Oncology PC-Elkhart
🇺🇸
Elkhart, Indiana, United States
Presence Saint Mary's Hospital
🇺🇸
Kankakee, Illinois, United States
Elkhart General Hospital
🇺🇸
Elkhart, Indiana, United States
Illinois CancerCare-Macomb
🇺🇸
Macomb, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸
Warrenville, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸
Galesburg, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸
Bloomington, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Springfield Clinic
🇺🇸
Springfield, Illinois, United States
IU Health La Porte Hospital
🇺🇸
La Porte, Indiana, United States
Illinois CancerCare-Princeton
🇺🇸
Princeton, Illinois, United States
Hematology Oncology Associates of Illinois-Highland Park
🇺🇸
Highland Park, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸
Eureka, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸
Ames, Iowa, United States
Memorial Hospital of South Bend
🇺🇸
South Bend, Indiana, United States
Michiana Hematology Oncology PC-South Bend
🇺🇸
South Bend, Indiana, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
Mary Greeley Medical Center
🇺🇸
Ames, Iowa, United States
Elkhart Clinic
🇺🇸
Elkhart, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸
Mishawaka, Indiana, United States
Reid Health
🇺🇸
Richmond, Indiana, United States
Constantinou, Costas L MD (UIA Investigator)
🇺🇸
Bettendorf, Iowa, United States
McFarland Clinic PC-Marshalltown
🇺🇸
Marshalltown, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸
Sioux City, Iowa, United States
Saint Joseph Regional Medical Center-Mishawaka
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Mishawaka, Indiana, United States
Lakeland Hospital
🇺🇸
Saint Joseph, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Ann Arbor Hematology -Oncology Associates
🇺🇸
Ypsilanti, Michigan, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Michiana Hematology Oncology PC-Plymouth
🇺🇸
Plymouth, Indiana, United States
Saint Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
McFarland Clinic PC-Boone
🇺🇸
Boone, Iowa, United States
South Bend Clinic
🇺🇸
South Bend, Indiana, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Mercy Health Saint Mary's
🇺🇸
Grand Rapids, Michigan, United States
Hematology Oncology Associates of Central New York-East Syracuse
🇺🇸
East Syracuse, New York, United States
Genesys Hurley Cancer Institute
🇺🇸
Flint, Michigan, United States
Bronson Battle Creek
🇺🇸
Battle Creek, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸
Duluth, Minnesota, United States
Mercy Health Mercy Campus
🇺🇸
Muskegon, Michigan, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Bixby Medical Center
🇺🇸
Adrian, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸
Grand Rapids, Michigan, United States
Saint Vincent Healthcare
🇺🇸
Billings, Montana, United States
Mercy Memorial Hospital
🇺🇸
Monroe, Michigan, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
Massachusetts General Hospital
🇺🇸
Charlestown, Massachusetts, United States
Lakeland Community Hospital
🇺🇸
Niles, Michigan, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Fairview-Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Hickman Cancer Center
🇺🇸
Adrian, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Lake Huron Medical Center
🇺🇸
Port Huron, Michigan, United States
Spectrum Health Reed City Hospital
🇺🇸
Reed City, Michigan, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Hematology Oncology Associates of Central New York-Auburn
🇺🇸
Auburn, New York, United States
Essentia Health Cancer Center
🇺🇸
Duluth, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Marie Yeager Cancer Center
🇺🇸
Saint Joseph, Michigan, United States
Parkland Health Center-Bonne Terre
🇺🇸
Bonne Terre, Missouri, United States
Strecker Cancer Center-Belpre
🇺🇸
Belpre, Ohio, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Saint Luke's Hospital of Duluth
🇺🇸
Duluth, Minnesota, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Columbus Oncology and Hematology Associates Inc
🇺🇸
Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Grant Medical Center
🇺🇸
Columbus, Ohio, United States
Lima Memorial Hospital
🇺🇸
Lima, Ohio, United States
Toledo Clinic Cancer Centers-Bowling Green
🇺🇸
Bowling Green, Ohio, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Montana Cancer Consortium NCORP
🇺🇸
Billings, Montana, United States
Wayne Memorial Hospital
🇺🇸
Goldsboro, North Carolina, United States
Delaware Radiation Oncology
🇺🇸
Delaware, Ohio, United States
Fairfield Medical Center
🇺🇸
Lancaster, Ohio, United States
Mount Carmel Health Center West
🇺🇸
Columbus, Ohio, United States
Doctors Hospital
🇺🇸
Columbus, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
OneHealth Marion General Hospital
🇺🇸
Marion, Ohio, United States
Hematology Oncology Associates of Central New York-Onondaga Hill
🇺🇸
Syracuse, New York, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
Kinston Medical Specialists PA
🇺🇸
Kinston, North Carolina, United States
The Mark H Zangmeister Center
🇺🇸
Columbus, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸
Toledo, Ohio, United States
Adena Regional Medical Center
🇺🇸
Chillicothe, Ohio, United States
Delaware Health Center-Grady Cancer Center
🇺🇸
Delaware, Ohio, United States
Grady Memorial Hospital
🇺🇸
Delaware, Ohio, United States
Community Medical Hospital
🇺🇸
Missoula, Montana, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
🇺🇸
Maumee, Ohio, United States
Columbus NCI Community Oncology Research Program
🇺🇸
Columbus, Ohio, United States
Samaritan North Health Center
🇺🇸
Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Marietta Memorial Hospital
🇺🇸
Marietta, Ohio, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸
Maumee, Ohio, United States
Oncology Hematology Care Inc-Healthplex
🇺🇸
Fairfield, Ohio, United States
Greenville Health System Cancer Institute-Butternut
🇺🇸
Greenville, South Carolina, United States
ProHealth Oconomowoc Memorial Hospital
🇺🇸
Oconomowoc, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸
New Richmond, Wisconsin, United States
ProHealth Waukesha Memorial Hospital
🇺🇸
Waukesha, Wisconsin, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Oncology Hematology Care Inc-Eden Park
🇺🇸
Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Mercy West
🇺🇸
Cincinnati, Ohio, United States
Oncology Hematology Care Inc - Anderson
🇺🇸
Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸
Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Blue Ash
🇺🇸
Cincinnati, Ohio, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸
Minneapolis, Minnesota, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Mount Zion
🇺🇸
San Francisco, California, United States
Cancer Center of Kansas - Fort Scott
🇺🇸
Fort Scott, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States
Cancer Center of Kansas-Manhattan
🇺🇸
Manhattan, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸
Winfield, Kansas, United States
Cancer Center of Kansas - Chanute
🇺🇸
Chanute, Kansas, United States
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Big Horn Basin Cancer Center
🇺🇸
Cody, Wyoming, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Missouri Baptist Medical Center
🇺🇸
Saint Louis, Missouri, United States
Capital Region Medical Center-Goldschmidt Cancer Center
🇺🇸
Jefferson City, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸
Sainte Genevieve, Missouri, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Hutchinson Area Health Care
🇺🇸
Hutchinson, Minnesota, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Miller-Dwan Hospital
🇺🇸
Duluth, Minnesota, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
🇺🇸
Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸
Woodbury, Minnesota, United States
Saint Joseph Hospital - Orange
🇺🇸
Orange, California, United States
Sharp Memorial Hospital
🇺🇸
San Diego, California, United States
Stamford Hospital/Bennett Cancer Center
🇺🇸
Stamford, Connecticut, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Delaware Clinical and Laboratory Physicians PA
🇺🇸
Newark, Delaware, United States
Helen F Graham Cancer Center
🇺🇸
Newark, Delaware, United States
Christiana Gynecologic Oncology LLC
🇺🇸
Newark, Delaware, United States
Michiana Hematology Oncology PC-Crown Point
🇺🇸
Crown Point, Indiana, United States
Community Howard Regional Health
🇺🇸
Kokomo, Indiana, United States
Michiana Hematology Oncology PC-Westville
🇺🇸
Westville, Indiana, United States
Oncology Associates at Mercy Medical Center
🇺🇸
Cedar Rapids, Iowa, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
McFarland Clinic PC-Trinity Cancer Center
🇺🇸
Fort Dodge, Iowa, United States
McFarland Clinic PC-Jefferson
🇺🇸
Jefferson, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Cancer Center of Kansas - El Dorado
🇺🇸
El Dorado, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸
Dodge City, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸
Newton, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸
Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸
Liberal, Kansas, United States
Cancer Center of Kansas - McPherson
🇺🇸
McPherson, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸
Parsons, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸
Wellington, Kansas, United States
Associates In Womens Health
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Wichita
🇺🇸
Wichita, Kansas, United States
Via Christi Regional Medical Center
🇺🇸
Wichita, Kansas, United States
Wichita NCI Community Oncology Research Program
🇺🇸
Wichita, Kansas, United States
Munson Medical Center
🇺🇸
Traverse City, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Baptist Health Corbin
🇺🇸
Corbin, Kentucky, United States
Baptist Health Madisonville/Merle Mahr Cancer Center
🇺🇸
Madisonville, Kentucky, United States
Baptist Health Paducah
🇺🇸
Paducah, Kentucky, United States
Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
Lafayette Family Cancer Center-EMMC
🇺🇸
Brewer, Maine, United States
Maine Center for Cancer Medicine-Scarborough
🇺🇸
Scarborough, Maine, United States
Centralia Oncology Clinic
🇺🇸
Centralia, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸
Galesburg, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸
Kewanee, Illinois, United States
Illinois Cancer Specialists-Niles
🇺🇸
Niles, Illinois, United States
Garneau, Stewart C MD (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, Illinois, United States
Saint Vincent Mercy Medical Center
🇺🇸
Toledo, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸
Tiffin, Ohio, United States
Mercy Saint Anne Hospital
🇺🇸
Toledo, Ohio, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
ProHealth D N Greenwald Center
🇺🇸
Mukwonago, Wisconsin, United States
Beaumont Hospital-Dearborn
🇺🇸
Dearborn, Michigan, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
Licking Memorial Hospital
🇺🇸
Newark, Ohio, United States
Newark Radiation Oncology
🇺🇸
Newark, Ohio, United States
Knox Community Hospital
🇺🇸
Mount Vernon, Ohio, United States
Saint Charles Hospital
🇺🇸
Oregon, Ohio, United States
Toledo Clinic Cancer Centers-Oregon
🇺🇸
Oregon, Ohio, United States
Southern Ohio Medical Center
🇺🇸
Portsmouth, Ohio, United States
Flower Hospital
🇺🇸
Sylvania, Ohio, United States
Springfield Regional Medical Center
🇺🇸
Springfield, Ohio, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
Toledo Community Hospital Oncology Program CCOP
🇺🇸
Toledo, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Fulton County Health Center
🇺🇸
Wauseon, Ohio, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
PinnacleHealth Cancer Center-Community Campus
🇺🇸
Harrisburg, Pennsylvania, United States
Greenville Health System Cancer Institute-Andrews
🇺🇸
Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Faris
🇺🇸
Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Greer
🇺🇸
Greer, South Carolina, United States
Greenville Health System Cancer Institute-Spartanburg
🇺🇸
Spartanburg, South Carolina, United States
Greenville Health System Cancer Institute-Seneca
🇺🇸
Seneca, South Carolina, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Fredericksburg Oncology Inc
🇺🇸
Fredericksburg, Virginia, United States
Gundersen Lutheran Medical Center
🇺🇸
La Crosse, Wisconsin, United States
Community Memorial Hospital
🇺🇸
Menomonee Falls, Wisconsin, United States
Rocky Mountain Oncology
🇺🇸
Casper, Wyoming, United States
Billings Clinic-Cody
🇺🇸
Cody, Wyoming, United States
Missouri Baptist Sullivan Hospital
🇺🇸
Sullivan, Missouri, United States
NorthShore University HealthSystem-Glenbrook Hospital
🇺🇸
Glenview, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Spector, David MD (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Saint Francis Regional Medical Center
🇺🇸
Shakopee, Minnesota, United States
Oncology Hematology Care Inc-Crestview
🇺🇸
Crestview Hills, Kentucky, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Hardin Memorial Hospital
🇺🇸
Elizabethtown, Kentucky, United States
Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
University Medical Center Brackenridge
🇺🇸
Austin, Texas, United States
Baptist Health Lexington
🇺🇸
Lexington, Kentucky, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Greenville Memorial Hospital
🇺🇸
Greenville, South Carolina, United States
Genesis Healthcare System Cancer Care Center
🇺🇸
Zanesville, Ohio, United States
Illinois CancerCare-Peru
🇺🇸
Peru, Illinois, United States
Radiation Oncology of Northern Illinois
🇺🇸
Ottawa, Illinois, United States
Lakeview Hospital
🇺🇸
Stillwater, Minnesota, United States
Saint Francis Medical Center
🇺🇸
Cape Girardeau, Missouri, United States
OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
🇺🇸
Pekin, Illinois, United States
Toledo Clinic Cancer Centers-Monroe
🇺🇸
Monroe, Michigan, United States
New Ulm Medical Center
🇺🇸
New Ulm, Minnesota, United States
Southeast Cancer Center
🇺🇸
Cape Girardeau, Missouri, United States
Missouri Baptist Outpatient Center-Sunset Hills
🇺🇸
Sunset Hills, Missouri, United States
Saint Ann's Hospital
🇺🇸
Westerville, Ohio, United States
Reading Hospital
🇺🇸
West Reading, Pennsylvania, United States