Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU
- Conditions
- Recurrent Breast CarcinomaStage IV Breast CancerBreast Carcinoma
- Interventions
- Registration Number
- NCT00520975
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase III trial studies first-line chemotherapy and trastuzumab to compare how well they work when given with or without bevacizumab in treating patients with breast cancer that overexpresses human epidermal growth factor receptor 2 (HER-2/NEU) and has spread to other areas of the body. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether giving first-line chemotherapy together with trastuzumab is more effective with or without bevacizumab in treating patients with metastatic breast cancer that overexpresses HER-2/NEU.
- Detailed Description
PRIMARY OBJECTIVES:
I. Evaluate efficacy of the addition of bevacizumab in patients eligible for first-line trastuzumab with chemotherapy for HER-2/NEU overexpressing metastatic breast cancer, by assessing the progression-free survival (PFS) after initiation of combination therapy.
SECONDARY OBJECTIVES:
I. Evaluate response rates (RR) in patients with measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\]), when applicable.
II. Evaluate overall survival (OS).
III. Evaluate the proportion of progression-free at 6 months.
IV. Compare the toxicity of chemotherapy/trastuzumab to that of chemotherapy/ trastuzumab in combination with bevacizumab.
V. Evaluate left ventricular ejection fraction (LVEF) decline and clinical congestive heart failure (CHF).
EXPLORATORY OBJECTIVES:
I. Compare breast cancer symptoms and treatment related symptoms between patients receiving chemotherapy and trastuzumab with or without bevacizumab.
II. Evaluate whether PFS correlates with vascular endothelial growth factor (VEGF) levels in breast tumor tissue.
III. Analysis of circulating tumor cells and circulating endothelial cells (CEC).
1. Serially enumerate circulating tumor cells (CTC) and CEC in patients on study and determine whether: the number of CTC and CEC decrease in responding patients; the extent of CTC and CEC decrease is greater in the experimental arm, Arm B versus the control arm, Arm A; enumeration of CTC and CEC in responding patients correlate with progression free survival (PFS).
2. Perform an exploratory analysis of phosphorylation status of v-akt murine thymoma viral oncogene homolog (akt)-2 in circulating tumor cells.
3. Perform an exploratory analysis of reverse transcriptase (RT)-polymerase chain reaction (PCR) of CTC messenger ribonucleic acid (mRNA) to determine whether change in expression of selected downstream targets of bevacizumab therapy can serve as pharmacodynamic or surrogate markers of bevacizumab targeting and modulation.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A:
INDUCTION THERAPY: Patients receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
ARM B:
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 10 years.
PROJECTED ACCRUAL: 489 patients
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 96
-
Histologically confirmed breast cancer that overexpresses HER-2/NEU with evidence of metastatic disease and/or chest wall recurrence prior to randomization
-
HER-2/NEU overexpression is defined as 3+ HER-2 positivity as measured by immunohistochemistry OR HER-2 gene amplification as measured by fluorescent in situ hybridization (FISH, e.g. Vysis), per American Society of Clinical Oncology guidelines
- NOTE: representative diagnostic tissue must be submitted for central diagnostic review for confirmation of HER-2/NEU overexpression within two weeks following patient randomization
-
Evaluable (measurable or non-measurable) disease is allowed if confirmed within 4 weeks prior to randomization
-
Prior endocrine treatment in the adjuvant or metastatic setting is allowed, provided last dose given >= 2 weeks prior to randomization
-
Radiation therapy is allowed provided last dose is given >= 3 weeks prior to randomization
-
Adjuvant trastuzumab therapy for breast cancer is allowed provided last dose was given >= 12 months prior to diagnosis of recurrence
-
Adjuvant or neoadjuvant taxane therapy for breast cancer is allowed provided last dose was given >= 12 months prior to diagnosis of recurrence
-
Adjuvant or neoadjuvant therapy with lapatinib is allowed provided last dose is given >= 4 weeks prior to diagnosis of recurrence
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Absolute neutrophil count >= 1,000/mm^3
-
Platelet count >= 100,000/mm^3
-
Total bilirubin =< 1.5 mg/dL
-
Aspartate aminotransferase (AST) =< 2 times upper limit of normal (ULN) (=< 5 times normal in patients with known liver involvement)
-
Serum creatinine =< 1.5 mg/dL
-
Urine protein: creatinine ratio =< 0.5 OR 24-hour urine protein < 1000 mg
-
International normalized ratio (INR) =< 1.5 X ULN
-
Partial thromboplastin time (PTT) =< 1.5 X ULN
-
Multi gated acquisition scan (MUGA) scan or echocardiogram (ECHO) within 6 weeks prior to randomization with an left ventricular ejection fraction (LVEF) above the institutional lower limit of normal
-
Patients must be able to understand and provide signed and dated written informed consent
-
Major surgical procedure within 4 weeks prior to randomization is not allowed (except for non-operative biopsy, which would not be considered major surgery); treatment can not begin until seven (7) days after placement of a vascular access device
-
Women must not be pregnant or breastfeeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to randomization to rule out pregnancy; women of childbearing potential and sexually active males must use an accepted and effective method of contraception
-
Patients on full-dose anticoagulants (e.g., warfarin) with PT/INR > 1.5 may be eligible provided that both of the following criteria are met:
- The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
- The patient has not active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
-
Patients with a concurrent active malignancy except carcinoma in situ of the cervix or non-melanoma skin cancers (unless disease-free for at least 5 years at study entry) are not allowed
-
Prior chemotherapy, trastuzumab, or bevacizumab for metastatic breast cancer
-
Patients who have had a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2 in the adjuvant or neo-adjuvant setting at any time
-
Patients with grade 2-4 neuropathy
-
Patients with a history or radiologic evidence of central nervous system (CNS) disease
-
Patients have a current non-healing wound or fracture
-
Patients have a hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies
-
Patients have a serious medical or psychiatric illness that would prevent ability to safely participate or provide informed consent
-
Patients using any of the following drugs known to inhibit platelet function are not eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal)
-
Clinically significant cardiovascular disease, including:
- History of cerebrovascular (CVA) within 6 months
- Uncontrolled hypertension
- Myocardial infarction or unstable angina within 6 months
- New York Heart Association class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
- Clinically significant peripheral vascular disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (chemotherapy and bevacizumab) Bevacizumab INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm A (chemotherapy and placebo) Placebo INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm A (chemotherapy and placebo) Trastuzumab INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm B (chemotherapy and bevacizumab) Trastuzumab INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm A (chemotherapy and placebo) Carboplatin INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm A (chemotherapy and placebo) Paclitaxel INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm B (chemotherapy and bevacizumab) Carboplatin INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Arm B (chemotherapy and bevacizumab) Paclitaxel INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years Progression-free survival (PFS) was defined as time from date of randomization to first disease progression, new second breast primaries, or to death from any cause, whichever occurred first, otherwise cases were censored at date last documented to be free of progression. Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the median PFS.
- Secondary Outcome Measures
Name Time Method Overall Survival assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. Kaplan-Meier method was used to estimate the median OS.
Proportion of Progression-free at 6 Months assessed at baseline, at 3 and 6 months after study entry Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Proportion of progression-free at 6 months was calculated using the Kaplan-Meier method.
Overall Response Rate assessed at baseline, every 12 weeks while on treatment, then very 3 months if patient is <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years from study entry until disease progression Overall response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).
Number of Patients Experiencing Congestive Heart Failure assessed every 3 months while on treatment and at 3 months post treatment Clinical congestive heart failure (CHF) was assessed using Left Ventricular Ejection Fraction (LVEF) and symptom information via the Cardiac Toxicity Form as well as symptom information collected via the Adverse Event Form. Clinical CHF was defined as symptomatic decline in LVEF to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction.
Trial Locations
- Locations (373)
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Fredericksburg Oncology Inc
🇺🇸Fredericksburg, Virginia, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Hematology and Oncology Associates
🇺🇸Chicago, Illinois, United States
NEA Baptist Memorial Hospital
🇺🇸Jonesboro, Arkansas, United States
Baton Rouge General Medical Center
🇺🇸Baton Rouge, Louisiana, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Hickman Cancer Center
🇺🇸Adrian, Michigan, United States
Memorial Hospital at Easton - Shore Regional Cancer Center
🇺🇸Easton, Maryland, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
York Hospital
🇺🇸York, Maine, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Bixby Medical Center
🇺🇸Adrian, Michigan, United States
The Memorial Hospital at Easton
🇺🇸Easton, Maryland, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Green Bay Oncology - Iron Mountain
🇺🇸Iron Mountain, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Green Bay Oncology - Escanaba
🇺🇸Escanaba, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸Flint, Michigan, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸Port Huron, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸Livonia, Michigan, United States
Mercy Memorial Hospital
🇺🇸Monroe, Michigan, United States
Toledo Clinic Cancer Centers-Monroe
🇺🇸Monroe, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Saint Mary's of Michigan
🇺🇸Saginaw, Michigan, United States
Montana Cancer Consortium NCORP
🇺🇸Billings, Montana, United States
Northern Rockies Radiation Oncology Center
🇺🇸Billings, Montana, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
Frontier Cancer Center and Blood Institute-Billings
🇺🇸Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸Great Falls, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Saint Peter's Community Hospital
🇺🇸Helena, Montana, United States
Northern Montana Hospital
🇺🇸Havre, Montana, United States
Glacier Oncology PLLC
🇺🇸Kalispell, Montana, United States
Community Medical Hospital
🇺🇸Missoula, Montana, United States
Kalispell Medical Oncology
🇺🇸Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Montana Cancer Specialists
🇺🇸Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸Missoula, Montana, United States
CHI Health Good Samaritan
🇺🇸Kearney, Nebraska, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
Portsmouth Regional Hospital
🇺🇸Portsmouth, New Hampshire, United States
Inspira Medical Center Vineland
🇺🇸Vineland, New Jersey, United States
Avera Saint Luke's Hospital and Cancer Center
🇺🇸Aberdeen, South Dakota, United States
University of Tennessee Health Science Center
🇺🇸Memphis, Tennessee, United States
West Virginia University Charleston
🇺🇸Charleston, West Virginia, United States
West Virginia University Healthcare
🇺🇸Morgantown, West Virginia, United States
Camden-Clark Memorial Hospital
🇺🇸Parkersburg, West Virginia, United States
Green Bay Oncology at Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Marshfield Clinic Cancer Center at Sacred Heart
🇺🇸Eau Claire, Wisconsin, United States
Green Bay Oncology - Oconto Falls
🇺🇸Oconto Falls, Wisconsin, United States
Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸Weston, Wisconsin, United States
Marshfield Clinic at James Beck Cancer Center
🇺🇸Rhinelander, Wisconsin, United States
Green Bay Oncology Limited at Saint Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
Saint Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
UW Cancer Center Johnson Creek
🇺🇸Johnson Creek, Wisconsin, United States
Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Marshfield Clinic-Rice Lake Center
🇺🇸Rice Lake, Wisconsin, United States
Saint Michael's Hospital
🇺🇸Stevens Point, Wisconsin, United States
Green Bay Oncology - Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Group Health Cooperative-Seattle
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Sidney and Lois Eskenazi Hospital
🇺🇸Indianapolis, Indiana, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Stoffel, Thomas J MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Saint Vincent Hospital and Health Care Center
🇺🇸Indianapolis, Indiana, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Center for Cancer Care and Research
🇺🇸Saint Louis, Missouri, United States
Orange Regional Medical Center
🇺🇸Middletown, New York, United States
Gaston Memorial Hospital
🇺🇸Gastonia, North Carolina, United States
Mercy Medical Center
🇺🇸Canton, Ohio, United States
Mary Rutan Hospital
🇺🇸Bellefontaine, Ohio, United States
Toledo Clinic Cancer Centers-Bowling Green
🇺🇸Bowling Green, Ohio, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
Margaret R Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
North Coast Cancer Care-Clyde
🇺🇸Clyde, Ohio, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Columbus NCI Community Oncology Research Program
🇺🇸Columbus, Ohio, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
Grady Memorial Hospital
🇺🇸Delaware, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Hematology Oncology Center Incorporated
🇺🇸Elyria, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Lima Memorial Hospital
🇺🇸Lima, Ohio, United States
Fairfield Medical Center
🇺🇸Lancaster, Ohio, United States
Saint Luke's Hospital
🇺🇸Maumee, Ohio, United States
Licking Memorial Hospital
🇺🇸Newark, Ohio, United States
Saint Charles Hospital
🇺🇸Oregon, Ohio, United States
Marietta Memorial Hospital
🇺🇸Marietta, Ohio, United States
Toledo Clinic Cancer Centers-Oregon
🇺🇸Oregon, Ohio, United States
North Coast Cancer Care
🇺🇸Sandusky, Ohio, United States
Springfield Regional Medical Center
🇺🇸Springfield, Ohio, United States
Flower Hospital
🇺🇸Sylvania, Ohio, United States
Mercy Hospital of Tiffin
🇺🇸Tiffin, Ohio, United States
The Toledo Hospital/Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Saint Vincent Mercy Medical Center
🇺🇸Toledo, Ohio, United States
Fulton County Health Center
🇺🇸Wauseon, Ohio, United States
Saint Ann's Hospital
🇺🇸Westerville, Ohio, United States
Doylestown Hospital
🇺🇸Doylestown, Pennsylvania, United States
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Pottstown Memorial Medical Center
🇺🇸Pottstown, Pennsylvania, United States
Penn State Health Saint Joseph Medical Center
🇺🇸Reading, Pennsylvania, United States
Grand View Hospital
🇺🇸Sellersville, Pennsylvania, United States
Zale Lipshy University Hospital
🇺🇸Dallas, Texas, United States
Hematology and Oncology Associates of Rhode Island Inc
🇺🇸Cranston, Rhode Island, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Kent County Hospital
🇺🇸Warwick, Rhode Island, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
🇺🇸Bremerton, Washington, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Minor and James Medical PLLC
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
The Polyclinic
🇺🇸Seattle, Washington, United States
Valley Medical Oncology Consultants-Castro Valley
🇺🇸Castro Valley, California, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
The Cancer Center of Hawaii-Liliha
🇺🇸Honolulu, Hawaii, United States
Mercy Capitol
🇺🇸Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Eden Hospital Medical Center
🇺🇸Castro Valley, California, United States
Bay Area Breast Surgeons Inc
🇺🇸Emeryville, California, United States
Valley Medical Oncology Consultants-Fremont
🇺🇸Fremont, California, United States
East Bay Radiation Oncology Center
🇺🇸Castro Valley, California, United States
Contra Costa Regional Medical Center
🇺🇸Martinez, California, United States
Saint Rose Hospital
🇺🇸Hayward, California, United States
Fremont - Rideout Cancer Center
🇺🇸Marysville, California, United States
Highland General Hospital
🇺🇸Oakland, California, United States
Community Hospital of Monterey Peninsula
🇺🇸Monterey, California, United States
Alta Bates Summit Medical Center - Summit Campus
🇺🇸Oakland, California, United States
Bay Area Tumor Institute
🇺🇸Oakland, California, United States
El Camino Hospital
🇺🇸Mountain View, California, United States
Hematology and Oncology Associates-Oakland
🇺🇸Oakland, California, United States
Tom K Lee Inc
🇺🇸Oakland, California, United States
Valley Care Health System - Pleasanton
🇺🇸Pleasanton, California, United States
Pomona Valley Hospital Medical Center
🇺🇸Pomona, California, United States
Valley Medical Oncology Consultants
🇺🇸Pleasanton, California, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸Galesburg, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Cottage
🇺🇸Galesburg, Illinois, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Hinsdale Hematology Oncology Associates Incorporated
🇺🇸Hinsdale, Illinois, United States
NorthShore Hematology Oncology-Libertyville
🇺🇸Libertyville, Illinois, United States
Midwest Center for Hematology Oncology
🇺🇸Joliet, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Garneau, Stewart C MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Sharis, Christine M MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Holy Family Medical Center
🇺🇸Monmouth, Illinois, United States
Illinois CancerCare-Monmouth
🇺🇸Monmouth, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Illinois Cancer Specialists-Niles
🇺🇸Niles, Illinois, United States
Spector, David MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸Naperville, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Hematology Oncology Associates of Illinois - Skokie
🇺🇸Skokie, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Saint Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Reid Hospital and Health Care Services
🇺🇸Richmond, Indiana, United States
IU Health La Porte Hospital
🇺🇸La Porte, Indiana, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Franciscan Saint Anthony Health-Michigan City
🇺🇸Michigan City, Indiana, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Saint Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
Stormont-Vail Regional Health Center
🇺🇸Topeka, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States
Saint Francis Hospital and Medical Center - Topeka
🇺🇸Topeka, Kansas, United States
Lakeland Hospital
🇺🇸St. Joseph, Michigan, United States
Fairview-Southdale Hospital
🇺🇸Edina, Minnesota, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Meeker County Memorial Hospital
🇺🇸Litchfield, Minnesota, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Mercy Hospital-Joplin
🇺🇸Joplin, Missouri, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Southeast Missouri Hospital
🇺🇸Cape Girardeau, Missouri, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Essentia Health Cancer Center
🇺🇸Duluth, Minnesota, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Saint Joseph's Hospital - Healtheast
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Cancer Research for the Ozarks NCORP
🇺🇸Springfield, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Mission Hospital-Memorial Campus
🇺🇸Asheville, North Carolina, United States
Cape Fear Valley Health System
🇺🇸Fayetteville, North Carolina, United States
Mount Carmel Health Center West
🇺🇸Columbus, Ohio, United States
Doctors Hospital
🇺🇸Columbus, Ohio, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸Maumee, Ohio, United States
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
🇺🇸Maumee, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
Penrose-Saint Francis Healthcare
🇺🇸Colorado Springs, Colorado, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Hospital District Sixth of Harper County
🇺🇸Anthony, Kansas, United States
Saint Alexius Medical Center
🇺🇸Bismarck, North Dakota, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Mid Dakota Clinic
🇺🇸Bismarck, North Dakota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Cancer Care Associates
🇺🇸Oklahoma City, Oklahoma, United States
Exempla Saint Joseph Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
Colorado Cancer Research Program NCORP
🇺🇸Denver, Colorado, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Western Oncology Research Consortium
🇺🇸Portland, Oregon, United States
Adventist Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
The Medical Center of Aurora
🇺🇸Aurora, Colorado, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium CCOP
🇺🇸Ann Arbor, Michigan, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Doctors Medical Center- JC Robinson Regional Cancer Center
🇺🇸San Pablo, California, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Saint Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸Grand Junction, Colorado, United States
Portneuf Medical Center
🇺🇸Pocatello, Idaho, United States
Heartland Cancer Research NCORP
🇺🇸Decatur, Illinois, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Saint Mary Corwin Medical Center
🇺🇸Pueblo, Colorado, United States
SCL Health Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
MacNeal Hospital and Cancer Center
🇺🇸Berwyn, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Emory University/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Memorial University Medical Center
🇺🇸Savannah, Georgia, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
🇺🇸Savannah, Georgia, United States
Franciscan St. Francis Health-Beech Grove
🇺🇸Beech Grove, Indiana, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
Illinois CancerCare-Havana
🇺🇸Havana, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
IU Health Arnett Cancer Care
🇺🇸Lafayette, Indiana, United States
Constantinou, Costas L MD (UIA Investigator)
🇺🇸Bettendorf, Iowa, United States
Hopedale Medical Complex - Hospital
🇺🇸Hopedale, Illinois, United States
Hematology Oncology Associates of Illinois-Highland Park
🇺🇸Highland Park, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸Joliet, Illinois, United States
Porubcin, Michael MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
DuPage Medical Group-Ogden
🇺🇸Naperville, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸Ames, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸Sioux City, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸Sioux City, Iowa, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Carle Clinic-Urbana Main
🇺🇸Urbana, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Community Cancer Center
🇺🇸Normal, Illinois, United States
Illinois CancerCare-Spring Valley
🇺🇸Spring Valley, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Community Howard Regional Health
🇺🇸Kokomo, Indiana, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
South Bend Clinic
🇺🇸South Bend, Indiana, United States
Genesis Medical Center - East Campus
🇺🇸Davenport, Iowa, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Genesis Medical Center - West Campus
🇺🇸Davenport, Iowa, United States
Northern Indiana Cancer Research Consortium CCOP
🇺🇸South Bend, Indiana, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Covenant Medical Center
🇺🇸Waterloo, Iowa, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Woodwinds Health Campus
🇺🇸Woodbury, Minnesota, United States
Capital Regional Medical Center
🇺🇸Jefferson City, Missouri, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
🇺🇸Saint Louis Park, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Erlanger Medical Center
🇺🇸Chattanooga, Tennessee, United States
Clements University Hospital
🇺🇸Dallas, Texas, United States
Genesis Healthcare System Cancer Care Center
🇺🇸Zanesville, Ohio, United States
Clinton Memorial Hospital
🇺🇸Wilmington, Ohio, United States
Greene Memorial Hospital
🇺🇸Xenia, Ohio, United States
Providence Milwaukie Hospital
🇺🇸Milwaukie, Oregon, United States
Interim LSU Public Hospital
🇺🇸New Orleans, Louisiana, United States
Louisiana State University Health Science Center
🇺🇸New Orleans, Louisiana, United States
Iowa-Wide Oncology Research Coalition NCORP
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Dean Hematology and Oncology Clinic
🇺🇸Madison, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸Wichita, Kansas, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Grandview Hospital
🇺🇸Dayton, Ohio, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Wichita NCI Community Oncology Research Program
🇺🇸Wichita, Kansas, United States
University of Rochester
🇺🇸Rochester, New York, United States
Interlakes Foundation Inc-Rochester
🇺🇸Rochester, New York, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Samaritan North Health Center
🇺🇸Dayton, Ohio, United States
Veteran Affairs Medical Center
🇺🇸Dayton, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸Dayton, Ohio, United States
Dayton NCI Community Oncology Research Program
🇺🇸Dayton, Ohio, United States
Toledo Community Hospital Oncology Program CCOP
🇺🇸Toledo, Ohio, United States
Mercy Saint Anne Hospital
🇺🇸Toledo, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸Toledo, Ohio, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Aspirus UW Cancer Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Danville Regional Medical Center
🇺🇸Danville, Virginia, United States