Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme

Phase 2

Completed

Conditions: Glioblastoma Multiforme

Interventions: Biological: bevacizumab
Other: placebo
Drug: dasatinib

Registration Number: NCT00892177

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also block the growth of the tumor by blocking blood flow to the tumor. It is not yet known whether bevacizumab together with dasatinib are more effective than a placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

PURPOSE: This randomized phase I/II trial (Phase I completed) is studying the side effects and best dose of dasatinib when given together with bevacizumab and to see how well it works compared to placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

Detailed Description: OUTLINE: This is a multicenter, phase I, dose-escalation study (Phase I completed) of dasatinib followed by a phase II randomized study. Patients are grouped according to study (1 vs 2). Patients in the phase II portion are stratified according to age (\> 70 years of age vs ≤ 70 years of age), and ECOG performance status (0 vs 1 or 2).

Phase I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral dasatinib once or twice daily on days 1-14 until the maximum-tolerated dose (MTD) is determined. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. (Phase I completed) Please see the Arms section for the Phase II treatment regimens.

OBJECTIVES:

PRIMARY OBJECTIVES:

1. Determine the maximum tolerated dose (MTD) of dasatinib in combination with bevacizumab in high grade glioma patients. (Phase I)

2. To assess the safety and adverse events of the dasatinib in combination with bevacizumab in this patient population. (Phase I)

3. To estimate the efficacy of the bevacizumab combination with dasatinib in recurrent glioblastoma multiforme as measured by progression free survival at six months and compare it with the efficacy of bevacizumab alone. (Phase II)

SECONDARY OBJECTIVES:

1. To describe the overall toxicity associated with the dasatinib/bevacizumab combination. (Phase I)

2. To describe any preliminary evidence of antitumor activity. (Phase I)

3. To assess the time to disease progression. (Phase II)

4. To assess the safety and toxicity of the bevacizumab combination with dasatinib in this patient population. (Phase II)

5. To estimate the efficacy of the bevacizumab combination with dasatinib in recurrent glioblastoma multiforme as measured by overall survival time and compare it with the efficacy of bevacizumab alone. (Phase II)

6. To assess the impact of the treatment on the patient's quality of life (QOL) using the overall score from the FACT-Br (Phase II)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 144

Inclusion Criteria

≥18 years of age
Study 1: Histologic confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review.
Study 2: Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review. NOTE: Variant gliosarcomas are eligible
Evidence of tumor progression by MRI or CT scan following RT or following the most recent anti-tumor therapy. Patients who had surgical treatment at recurrence are eligible if there is imaging evidence of disease progression as compared to the first postoperative scan.
Bidimensionally measurable or evaluable disease by MRI or CT scan.
ECOG Performance Status (PS) 0, 1, or 2.
Patient willing to discontinue use of aspirin or medications that inhibit platelet function ≥ 1 week prior to registration.
Previous RT and ≥12 weeks since the completion of RT prior to registration.
The following laboratory values obtained ≤ 21 days prior to registration.
- ANC ≥1500
- PLT ≥100,000
- Hgb >9.0 g/dL
- T. bili ≤1.5 x ULN
- SGOT (AST) ≤ 3 x ULN
- Creatinine ≤ ULN
UPC ratio <1. NOTE: Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio ≥1.0, 24-hour urine protein must be obtained and the level should be <1000 mg
Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
Ability to complete questionnaire(s) by themselves or with assistance.
Provide informed written consent
Willingness to return to enrolling institution for follow-up.
Patient willing to provide mandatory tissue samples for research purposes
Study 1: Any number of prior chemotherapy regimens for recurrent disease. Study 2: Up to 2 prior chemotherapy regimens with ≤1 regimen for recurrent disease.

III.

Exclusion Criteria

Pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception during this study and for up to 6 months after bevacizumab treatment has ended. NOTE: bevacizumab and dasatinib are investigational agents whose genotoxic effects on the developing fetus and newborn are unknown.
Prior intratumoral therapy, stereotactic radiosurgery, or interstitial brachytherapy.

EXCEPTION: Separate lesion on MRI which is not part of the previous treatment field, or convincing evidence of recurrent disease, based on biopsy, MRI spectroscopy, or PET scan.
Prior treatment with bevacizumab or VEGF-Trap (Aflibercept).
Inadequately controlled hypertension (systolic blood pressure of >150 mmHg or diastolic pressure >100 mmHg on anti-hypertensive medications).

NOTE: Patients with well-controlled hypertension are eligible.
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 toxicity of the prescribed regimens.
Immunocompromised patients (other than that related to the use of corticosteroids). NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this study.
Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption) that impairs ability to swallow pills.
Receiving therapeutic anticoagulation with Warfarin. NOTE: Prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices is allowed, provided that INR <1.5. Therapeutic anti-coagulation with low molecular weight heparin is allowed at time of registration.
Evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
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.
History of myocardial infarction or unstable angina ≤6 months prior to registration.
New York Heart Association (NYHA) classification II, III or IV congestive heart failure.
Core biopsy or other minor surgical procedures ≤7 days prior to registration. Note: Placement of a vascular access device is allowed.
Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to registration or anticipation of need for major surgical procedure during the course of the study.
Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis ≤6 months prior to registration.
History of hypertensive crisis or hypertensive encephalopathy.
Known hypersensitivity to any of the components of dasatinib or bevacizumab.
Serious, non-healing wound, active ulcer, or untreated bone fracture
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤6 months prior to registration.
Active or recent history of hemoptysis (≥ ½ teaspoon of bright red blood per episode) ≤30 days prior to registration.
History of stroke or transient ischemic attack (TIA) ≤6 months prior to registration.
Any evidence of CNS hemorrhage on baseline CT or MRI
Any of the following Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes ≤7 days prior to registration (patients must discontinue drug 7 days prior to starting dasatinib)
- Quinidine, procainamide, disopyramide
- Amiodarone, sotalol, ibutilide, dofetilide
- Erythromycin, clarithromycin
- Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
- Prochlorperazine
Diagnosed congenital long QT syndrome
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)
Prolonged QTc interval on pre-entry electrocardiogram (>450 msec)
Patients may not have any clinically significant cardiovascular disease including the following:
- Myocardial infarction or ventricular tachyarrhythmia within 6 months.
- Prolonged QTc ≥ 480 msec (Fridericia correction)
- Ejection fraction less than institutional normal
- Major conduction abnormality (unless a cardiac pacemaker is present)
Note: Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (ECG) to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator. Patients with underlying cardiopulmonary dysfunction should be excluded from the study.
Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
Known pleural or pericardial effusion of any grade
Concomitant use of H2 blockers or proton pump inhibitors that cannot be discontinued or switched to locally acting agents (i.e. famotidine or omeprazole.)
Use of the following Enzyme Inducing Anti-Convulsive (EIAC) medications is prohibited ≤ 7 days prior to registration: carbamazepine (Tegretol®, Tegretol XR®, Carbatrol®), phenytoin (Dilantin®, Phenytek®), fosphenytoin (Cerebyx®), phenobarbital, pentobarbital and primidone (Mysoline®). Note: Many antiepileptic drugs induce hepatic enzymes. Because dasatinib is metabolized by hepatic enzymes, patients taking antiepileptic medications that induce hepatic enzymes (EIACs) are ineligible for this trial. To be eligible for this trial, patients taking EIACs must be switched to non-EIACs ≥ 7 days prior to registration. The following agents are not known to affect dasatinib metabolism and are acceptable for use: valproic acid (Depakote®, Depacon®), gabapentin (Neurontin®), lamotrigine (Lamictal®), topiramate (Topamax®), tiagabine (Gabitril®), zonisamide (Zonegran®), levetiracetam (Keppra®), clonazepam (Klonopin®) and clobazam (Frisium®).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II	placebo	Patients receive bevacizumab on Day 1 and placebo on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm I	bevacizumab	Patients receive bevacizumab on Day 1 and dasatinib on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II	bevacizumab	Patients receive bevacizumab on Day 1 and placebo on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm I	dasatinib	Patients receive bevacizumab on Day 1 and dasatinib on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Bevacizumab (Phase I)	14 days	The Maximum Tolerated Dose (MTD) will be based on the assessment of dose-limiting toxicities (DLT) during the first 4 weeks of treatment only (i.e., following the first 2 treatment cycles), and will be defined as the dose at which fewer than one-third of patients experience a DLT to study treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with the next higher dose having at least 2 out of 3 or 2 out of 6 patients encountering DLT.\> Three patients will be treated at each dose level, and can be enrolled simultaneously. If one DLT is encountered, an additional 3 patients will be added to that dose level. If at any point two DLTs are encountered within a given dose level, then the MTD has been exceeded and if only three patients have been treated at the next lower dose three more patients are treated at the next lower dose. The number of patients who developed DLTs are reported here by dose level, with the MTD reported in the statistical analysis section.
Progression-free Survival at 6 Months (PFS6) (Phase II)	6 months	The primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation (PFS6). All eligible consented patients that received treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. 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. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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. The PFS6 will be estimated as the number of evaluable patients progression free and still alive at 6 months divided by the total number of evaluable patients. The confidence interval will be calculated according to the Clopper-Pearson Method.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 (Phase II)	Up to 3 years	Adverse events were collected systematically at the end of each cycle and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. Events are scored as: 1="Mild symptoms", 2= "Moderate", 3="Severe", 4="Life-threatening", and 5="Death". The number of patients reporting a grade 3 or higher event regardless of attribution are summarized here. A complete list of all adverse events reported during treatment can be found in the Adverse Events Section.
Overall Survival (Phase II)	Up to 3 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 arms of the study will be estimated using the Kaplan-Meier method, and be compared using log-rank tests.
Time-to-disease Progression (Phase II)	Up to 3 years	Time-to-disease progression is defined as the time from start of study therapy 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 unless there is documented evidence that no progression occurred before 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. Patients who experience major treatment violations will be censored for progression on the date the treatment violation occurred. The time-to-progression distribution will be estimated using the Kaplan-Meier method.
Objective Response (Phase II)	Up to 3 years	Objective response to treatment will be determined by the results of neurological exam and the MRI and/or CT measurement of the tumor at each evaluation as is used for all NCCTG neuro-oncology trials. The percentage of patients in each response category will be summarized, 95% confidence intervals calculated, and rates between the 2 arms will be compared using a Fisher's Exact test. For bi-dimensionally measurable disease, CR: total disappearance of all tumor and that patients be on no corticosteroids or on only adrenal replacement maintenance; PR: ≥ 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions, and stable or decreasing steroid dosing; PD: \>25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions; REGR: unequivocal reduction in extent of contrast-enhancement, or a decrease in mass effect, no new lesions (for evaluable disease); SD: failure to qualify for CR, PR,REGR or PD.
Patient-reported QOL, as Measure by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) (Phase II)	Baseline to cycle 10 (20 weeks).	FACT-Br questionnaires were used to assess QOL at every other cycle of treatment (prior to cycles 3, 5, 7, etc.). FACT-Br includes 50 questions used to assess patients' self-assessment in 4 broad categories: Physical, Social/Family, Emotional, and Function Well-being. Scores range from 0="Not at all", 1="A little bit", 2="Somewhat", 3="Quite a bit", 4="Very Much". Higher scores can be interpreted as having higher quality of life. The scores for all 50 questions were summed to give a total score per patient per cycle. Therefore the possible range is from 0 to 200. Below is the reported mean and standard deviation for patients at baseline and during cycles 2, 4, 6, 8, and 10.

Trial Locations

Locations (303): Kauai Medical Clinic
🇺🇸
Lihue, Hawaii, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸
Lihue, Hawaii, United States
Castle Medical Center
🇺🇸
Kailua, Hawaii, United States
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
🇺🇸
Boise, Idaho, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸
Pekin, Illinois, United States
Illinois CancerCare - Canton
🇺🇸
Canton, Illinois, United States
Illinois CancerCare - Havana
🇺🇸
Havana, Illinois, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
BroMenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Community Hospital of Ottawa
🇺🇸
Ottawa, Illinois, United States
Illinois CancerCare - Pekin
🇺🇸
Pekin, Illinois, United States
McFarland Clinic, PC
🇺🇸
Ames, Iowa, United States
Eureka Community Hospital
🇺🇸
Eureka, Illinois, United States
Illinois CancerCare - Eureka
🇺🇸
Eureka, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare - Bloomington
🇺🇸
Bloomington, Illinois, United States
Illinois CancerCare - Community Cancer Center
🇺🇸
Normal, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, Illinois, United States
Galesburg Clinic, PC
🇺🇸
Galesburg, Illinois, United States
Illinois CancerCare - Kewanee Clinic
🇺🇸
Kewanee, Illinois, United States
Reid Hospital & Health Care Services
🇺🇸
Richmond, Indiana, United States
Cancer Center of Kansas - Chanute
🇺🇸
Chanute, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸
Dodge City, Kansas, United States
Illinois CancerCare - Monmouth
🇺🇸
Monmouth, Illinois, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸
El Dorado, Kansas, United States
Illinois CancerCare - Spring Valley
🇺🇸
Spring Valley, Illinois, United States
Methodist West Hospital
🇺🇸
West Des Moines, Iowa, United States
Illinois CancerCare - Peru
🇺🇸
Peru, Illinois, United States
Oncology Associates at Mercy Medical Center
🇺🇸
Cedar Rapids, Iowa, United States
Community Cancer Center
🇺🇸
Elyria, Ohio, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸
Kingman, Kansas, United States
Rush-Copley Cancer Care Center
🇺🇸
Aurora, Illinois, United States
Illinois CancerCare - Carthage
🇺🇸
Carthage, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸
Ottawa, Illinois, United States
Mercy Cancer Center at Mercy Medical Center - North Iowa
🇺🇸
Mason City, Iowa, United States
Illinois CancerCare - Princeton
🇺🇸
Princeton, Illinois, United States
Harold Alfond Center for Cancer Care
🇺🇸
Augusta, Maine, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸
Chanute, Kansas, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸
Sioux City, Iowa, United States
Medical Oncology and Hematology Associates - West Des Moines
🇺🇸
Clive, Iowa, United States
Mercy Medical Center - Sioux City
🇺🇸
Sioux City, Iowa, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸
Wellington, Kansas, United States
St. Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Cancer Center of Kansas - El Dorado
🇺🇸
El Dorado, Kansas, United States
Bixby Medical Center
🇺🇸
Adrian, Michigan, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸
Maplewood, Minnesota, United States
Minnesota Oncology - Maplewood
🇺🇸
Maplewood, Minnesota, United States
Toledo Clinic Cancer Centers-Monroe
🇺🇸
Monroe, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
CancerCare of Maine at Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
Essentia Health - Duluth Clinic
🇺🇸
Duluth, Minnesota, United States
Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
CCOP - Duluth
🇺🇸
Duluth, Minnesota, United States
St. Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Toledo Clinic Cancer Centers-Adrian
🇺🇸
Adrian, Michigan, United States
Nebraska Cancer Research Center
🇺🇸
Lincoln, Nebraska, United States
Foote Memorial Hospital
🇺🇸
Jackson, Michigan, United States
Sparrow Regional Cancer Center
🇺🇸
Lansing, Michigan, United States
Community Cancer Center of Monroe
🇺🇸
Monroe, Michigan, United States
Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸
Robbinsdale, Minnesota, United States
CentraCare Clinic - River Campus
🇺🇸
Saint Cloud, Minnesota, United States
Oakwood Cancer Center at Oakwood Hospital and Medical Center
🇺🇸
Dearborn, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸
Grosse Pointe Woods, Michigan, United States
St. Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
St. John Macomb Hospital
🇺🇸
Warren, Michigan, United States
Seton Cancer Institute at Saint Mary's - Saginaw
🇺🇸
Saginaw, Michigan, United States
Hutchinson Area Health Care
🇺🇸
Hutchinson, Minnesota, United States
Sanford Clinic North-Bemidji
🇺🇸
Bemidji, Minnesota, United States
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
🇺🇸
Concord, New Hampshire, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Mount Kisco Medical Group at Northern Westchester Hospital
🇺🇸
Mount Kisco, New York, United States
Fairview Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Toledo Hospital
🇺🇸
Toledo, Ohio, United States
MeritCare Bemidji
🇺🇸
Bemidji, Minnesota, United States
Toledo Clinic - Oregon
🇺🇸
Oregon, Ohio, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Mercy Memorial Hospital - Monroe
🇺🇸
Monroe, Michigan, United States
Frontier Cancer Center and Blood Institutes-Billings
🇺🇸
Billings, Montana, United States
Mercy Regional Cancer Center at Mercy Hospital
🇺🇸
Port Huron, Michigan, United States
Billings Clinic - Downtown
🇺🇸
Billings, Montana, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Miller - Dwan Medical Center
🇺🇸
Duluth, Minnesota, United States
Blanchard Valley Medical Associates
🇺🇸
Findlay, Ohio, United States
Legacy Mount Hood Medical Center
🇺🇸
Gresham, Oregon, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
Charles F. Kettering Memorial Hospital
🇺🇸
Kettering, Ohio, United States
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
🇺🇸
Xenia, Ohio, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Mercy Hospital of Tiffin
🇺🇸
Tiffin, Ohio, United States
Wayne Memorial Hospital, Incorporated
🇺🇸
Goldsboro, North Carolina, United States
Grandview Hospital
🇺🇸
Dayton, Ohio, United States
UVMC Cancer Care Center at Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Flower Hospital Cancer Center
🇺🇸
Sylvania, Ohio, United States
Legacy Meridian Park Hospital
🇺🇸
Tualatin, Oregon, United States
CCOP - Dayton
🇺🇸
Dayton, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸
Toledo, Ohio, United States
Lima Memorial Hospital
🇺🇸
Lima, Ohio, United States
Fulton County Health Center
🇺🇸
Wauseon, Ohio, United States
Sanford Roger Maris Cancer Center
🇺🇸
Fargo, North Dakota, United States
Wood County Oncology Center
🇺🇸
Bowling Green, Ohio, United States
Precision Radiotherapy at University Pointe
🇺🇸
West Chester, Ohio, United States
Toledo Clinic, Incorporated - Main Clinic
🇺🇸
Toledo, Ohio, United States
St. Charles Mercy Hospital
🇺🇸
Oregon, Ohio, United States
Northwest Ohio Oncology Center
🇺🇸
Maumee, Ohio, United States
Geisinger Medical Group
🇺🇸
State College, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Cancer Centers of the Carolinas - Faris Road
🇺🇸
Greenville, South Carolina, United States
Waukesha Memorial Hospital Regional Cancer Center
🇺🇸
Waukesha, Wisconsin, United States
Legacy Salmon Creek Hospital
🇺🇸
Vancouver, Washington, United States
Cancer Centers of the Carolinas - Seneca
🇺🇸
Seneca, South Carolina, United States
Greenville Health System Cancer Institute-Butternut
🇺🇸
Greenville, South Carolina, United States
Regional Cancer Center at Oconomowoc Memorial Hospital
🇺🇸
Oconomowoc, Wisconsin, United States
Greenville Hospital Cancer Center
🇺🇸
Greenville, South Carolina, United States
CCOP - Greenville
🇺🇸
Greenville, South Carolina, United States
Westfields Hospital/Cancer Center of Western Wisconsin
🇺🇸
New Richmond, Wisconsin, United States
Cancer Centers of the Carolinas - Greer Medical Oncology
🇺🇸
Greer, South Carolina, United States
Gundersen Lutheran Center for Cancer and Blood
🇺🇸
La Crosse, Wisconsin, United States
Fredericksburg Oncology, Incorporated
🇺🇸
Fredericksburg, Virginia, United States
Oconomowoc Memorial Hospital-ProHealth Care Inc
🇺🇸
Oconomowoc, Wisconsin, United States
Union Hospital of Cecil County
🇺🇸
Elkton, Maryland, United States
Cancer Care Associates - Norman
🇺🇸
Norman, Oklahoma, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
CCOP - Montana Cancer Consortium
🇺🇸
Billings, Montana, United States
Willmar Cancer Center at Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸
La Jolla, California, United States
Palchak David MD
🇺🇸
Pismo Beach, California, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸
Colorado Springs, Colorado, United States
North Colorado Medical Center
🇺🇸
Greeley, Colorado, United States
Sky Ridge Medical Center
🇺🇸
Lone Tree, Colorado, United States
Hope Cancer Care Center at Longmont United Hospital
🇺🇸
Longmont, Colorado, United States
McKee Medical Center
🇺🇸
Loveland, Colorado, United States
St. Mary - Corwin Regional Medical Center
🇺🇸
Pueblo, Colorado, United States
Exempla Lutheran Medical Center
🇺🇸
Wheat Ridge, Colorado, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
🇺🇸
Fort Lauderdale, Florida, United States
Memorial Cancer Institute at Memorial Regional Hospital
🇺🇸
Hollywood, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
🇺🇸
Jupiter, Florida, United States
CCOP - Mount Sinai Medical Center
🇺🇸
Miami Beach, Florida, United States
John B Amos Cancer Center
🇺🇸
Columbus, Georgia, United States
Oncare Hawaii, Incorporated - Pali Momi
🇺🇸
'Aiea, Hawaii, United States
Mercy Medical Center-West Lakes
🇺🇸
West Des Moines, Iowa, United States
Toledo Clinic Cancer Centers - Adrian
🇺🇸
Adrian, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸
Duluth, Minnesota, United States
Regions Hospital Cancer Care Center
🇺🇸
Saint Paul, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸
Saint Louis Park, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸
Shakopee, Minnesota, United States
Lakeview Hospital
🇺🇸
Stillwater, Minnesota, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
🇺🇸
Missoula, Montana, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Kinston Medical Specialists
🇺🇸
Kinston, North Carolina, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
St. Vincent Mercy Medical Center
🇺🇸
Toledo, Ohio, United States
Medical University of Ohio Cancer Center
🇺🇸
Toledo, Ohio, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
St. Francis Hospital Cancer Care Services
🇺🇸
Indianapolis, Indiana, United States
University Medical Center of Southern Nevada
🇺🇸
Las Vegas, Nevada, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸
Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Hennepin County Medical Center - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
Cancer Center of Kansas - Newton
🇺🇸
Newton, Kansas, United States
Associates in Women's Health - Wichita
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸
Wichita, Kansas, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸
Pratt, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸
Parsons, Kansas, United States
Associates in Womens Health, PA - North Review
🇺🇸
Wichita, Kansas, United States
CCOP - Wichita
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸
Dodge City, Kansas, United States
Cancer Center of Kansas, PA - Liberal
🇺🇸
Liberal, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸
Winfield, Kansas, United States
Kapiolani Medical Center at Pali Momi
🇺🇸
'Aiea, Hawaii, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
Cancer Center of Kansas, PA - Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸
Wichita, Kansas, United States
Wesley Medical Center
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸
Newton, Kansas, United States
Cancer Center of Kansas, PA - Salina
🇺🇸
Salina, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸
Fort Scott, Kansas, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸
Wichita, Kansas, United States
Dakota Cancer Institute at Dakota Clinic - South University
🇺🇸
Fargo, North Dakota, United States
Essentia Health Cancer Center-South University Clinic
🇺🇸
Fargo, North Dakota, United States
Sanford Bismarck Medical Center
🇺🇸
Bismarck, North Dakota, United States
Sanford Medical Center-Fargo
🇺🇸
Fargo, North Dakota, United States
Altru Cancer Center at Altru Hospital
🇺🇸
Grand Forks, North Dakota, United States
MeritCare Broadway
🇺🇸
Fargo, North Dakota, United States
Sanford Clinic North-Fargo
🇺🇸
Fargo, North Dakota, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸
Voorhees, New Jersey, United States
St. Vincent Healthcare Cancer Care Services
🇺🇸
Billings, Montana, United States
Montana Cancer Specialists at Montana Cancer Center
🇺🇸
Missoula, Montana, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
🇺🇸
Grand Island, Nebraska, United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
🇺🇸
Hartford, Connecticut, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Nevada Cancer Research Foundation CCOP
🇺🇸
Las Vegas, Nevada, United States
Billings Clinic
🇺🇸
Billings, Montana, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
St. James Healthcare Cancer Care
🇺🇸
Butte, Montana, United States
St. Peter's Hospital
🇺🇸
Helena, Montana, United States
New Hampshire Oncology - Hematology, PA - Hooksett
🇺🇸
Hooksett, New Hampshire, United States
Lakes Region General Hospital
🇺🇸
Laconia, New Hampshire, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
🇺🇸
Billings, Montana, United States
CCOP - Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
Callahan Cancer Center at Great Plains Regional Medical Center
🇺🇸
North Platte, Nebraska, United States
Benefis Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
Cancer Resource Center - Lincoln
🇺🇸
Lincoln, Nebraska, United States
Benefis Healthcare - Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
New Hampshire Oncology-Hematology PA
🇺🇸
Concord, New Hampshire, United States
McLeod Regional Medical Center
🇺🇸
Florence, South Carolina, United States
Valley Hospital - Ridgewood
🇺🇸
Ridgewood, New Jersey, United States
Cancer Centers of the Carolinas - Spartanburg
🇺🇸
Spartanburg, South Carolina, United States
Bozeman Deaconess Cancer Center
🇺🇸
Bozeman, Montana, United States
Greenville Health System Cancer Institute-Seneca
🇺🇸
Seneca, South Carolina, United States
Greenville Health System Cancer Institute-Spartanburg
🇺🇸
Spartanburg, South Carolina, United States
Cancer Centers of the Carolinas - Grove Commons
🇺🇸
Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Faris
🇺🇸
Greenville, South Carolina, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
Sanford Cancer Center Oncology Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Alegent Health Lakeside Hospital
🇺🇸
Omaha, Nebraska, United States
Lakeside Hospital
🇺🇸
Omaha, Nebraska, United States
Creighton University Medical Center
🇺🇸
Omaha, Nebraska, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
St. Anthony Central Hospital
🇺🇸
Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸
Denver, Colorado, United States
St. Joseph Hospital
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸
Omaha, Nebraska, United States
Immanuel Medical Center
🇺🇸
Omaha, Nebraska, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
🇺🇸
Omaha, Nebraska, United States
Cancer Care Associates - Mercy Campus
🇺🇸
Oklahoma City, Oklahoma, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸
Portland, Oregon, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
New Ulm Medical Center
🇺🇸
New Ulm, Minnesota, United States
Coborn Cancer Center
🇺🇸
Saint Cloud, Minnesota, United States
Mayo Clinic Cancer Center
🇺🇸
Rochester, Minnesota, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸
Saint Louis Park, Minnesota, United States
Minnesota Oncology - Woodbury
🇺🇸
Woodbury, Minnesota, United States
Aurora Presbyterian Hospital
🇺🇸
Aurora, Colorado, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Illinois CancerCare - Macomb
🇺🇸
Macomb, Illinois, United States
Good Samaritan Hospital
🇺🇸
Dayton, Ohio, United States
Hematology Oncology Center
🇺🇸
Elyria, Ohio, United States
Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
Geisinger Medical Center-Cancer Center Hazelton
🇺🇸
Hazleton, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Medcenter One Hospital Cancer Care Center
🇺🇸
Bismarck, North Dakota, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
St. Alexius Medical Center Cancer Center
🇺🇸
Bismarck, North Dakota, United States
Mid Dakota Clinic, PC
🇺🇸
Bismarck, North Dakota, United States
Saint Joseph Mercy Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
St. Anne Mercy Hospital
🇺🇸
Toledo, Ohio, United States
Cancer Research Center of Hawaii
🇺🇸
Honolulu, Hawaii, United States
Oncare Hawaii Inc-POB II
🇺🇸
Honolulu, Hawaii, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
David L. Rike Cancer Center at Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Samaritan North Cancer Care Center
🇺🇸
Dayton, Ohio, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
OnCare Hawaii, Incorporated - Lusitana
🇺🇸
Honolulu, Hawaii, United States
University of Hawaii
🇺🇸
Honolulu, Hawaii, United States
OnCare Hawaii, Incorporated - Kuakini
🇺🇸
Honolulu, Hawaii, United States
Mercy Cancer Center at Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Queen's Cancer Institute at Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
Straub Clinic and Hospital, Incorporated
🇺🇸
Honolulu, Hawaii, United States
Kuakini Medical Center
🇺🇸
Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
CCOP - Iowa Oncology Research Association
🇺🇸
Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at Mercy Cancer Center
🇺🇸
Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸
Peoria, Illinois, United States
Avera Cancer Institute
🇺🇸
Sioux Falls, South Dakota, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸
Sioux Falls, South Dakota, United States
Mayo Clinic Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸
Ottawa, Illinois, United States
Illinois Valley Community Hospital
🇺🇸
Peru, Illinois, United States
Cedar Rapids Oncology Association
🇺🇸
Cedar Rapids, Iowa, United States
Mercy Hospital
🇺🇸
Cedar Rapids, Iowa, United States
Mercy Cancer Center - West Lakes
🇺🇸
Clive, Iowa, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸
Winfield, Kansas, United States
Hickman Cancer Center at Bixby Medical Center
🇺🇸
Adrian, Michigan, United States
Cancer Center of Kansas - Wellington
🇺🇸
Wellington, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸
Parsons, Kansas, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States