Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
- Conditions
- PineoblastomaRecurrent MedulloblastomaRefractory Peripheral Primitive Neuroectodermal TumorRecurrent Primitive Neuroectodermal TumorRefractory MedulloblastomaCentral Nervous System Neoplasm
- Interventions
- Registration Number
- NCT01217437
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This randomized phase II trial studies how well giving temozolomide and irinotecan hydrochloride together with or without bevacizumab works in treating young patients with recurrent or refractory medulloblastoma or central nervous system (CNS) primitive neuroectodermal tumors. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, 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 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. It is not yet known whether temozolomide and irinotecan hydrochloride are more effective with or without bevacizumab in treating medulloblastoma or CNS primitive neuroectodermal tumors.
- Detailed Description
PRIMARY OBJECTIVES:
l. To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan (irinotecan hydrochloride), and bevacizumab for recurrent medulloblastoma (MB)/primitive neuroectodermal tumor (PNET) of childhood.
SECONDARY OBJECTIVES:
I. To assess the response rate for each treatment arm amongst patients who are enrolled with measurable disease.
II. To determine event-free survival (EFS) for each patient compared across regimens.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive temozolomide orally (PO) and irinotecan hydrochloride IV over 90 minutes on days 1-5.
ARM II: Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.
In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 108
-
Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
-
Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence
-
Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters
-
All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment
-
Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age)
-
Patients must have a life expectancy of >= 8 weeks
-
Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible
-
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
-
Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea)
-
Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies
-
External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry
-
Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry
-
Study specific limitations on prior therapy:
- Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor
- Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry
-
-
Patients must have recovered from any surgical procedure before enrolling on this study:
-
Patients with a major surgical procedure within 28 days prior to enrollment should be excluded
-
Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded
-
For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed
-
There should be no anticipation of need for major surgical procedures during the course of the study
-
Examples of major, intermediate, or minor surgical procedures:
- Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy
- Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy
- Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis
-
-
Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy
-
-
Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication
-
Concomitant medications restrictions:
- Growth factor(s): Must not have received within 7 days of entry onto this study
- Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days
- Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day
-
Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days)
-
Platelet count >= 100,000/uL (transfusion independent)
-
Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions)
-
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows:
- =< 0.4 mg/dL (for patients aged 1 month to < 6 months)
- =< 0.5 mg/dL (for patients aged 6 months to < 1 year)
- =< 0.6 mg/dL (for patients aged 1 to < 2 years)
- =< 0.8 mg/dL (for patients aged 2 to < 6 years)
- =< 1 mg/dL (for patients aged 6 to < 10 years)
- =< 1.2 mg/dL (for patients aged 10 to < 13 years)
- =< 1.4 mg/dL (for female patients aged >= 13 years)
- =< 1.5 mg/dL (for male patients aged 13 to < 16 years)
- =< 1.7 mg/dL (for male patients aged >= 16 years)
-
Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment
-
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
-
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age
-
Central nervous system function defined as
- Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
-
Adequate coagulation defined as
- International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal
- Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study
- Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry
- Patients must not have a known bleeding diathesis or coagulopathy
- Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry
- Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history
- Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment
- Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible
- Patients must not have serious and inadequately controlled cardiac arrhythmia
- Female patients who are pregnant are not eligible for this study
- Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
- Female patients of childbearing potential must have a negative pregnancy test
- Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II (temozolomide, irinotecan hydrochloride, bevacizumab) Bevacizumab Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15. Arm I (temozolomide, irinotecan hydrochloride) Irinotecan Hydrochloride Patients receive temozolomide PO and irinotecan hydrochloride IV over 90 minutes on days 1-5. Arm I (temozolomide, irinotecan hydrochloride) Temozolomide Patients receive temozolomide PO and irinotecan hydrochloride IV over 90 minutes on days 1-5. Arm II (temozolomide, irinotecan hydrochloride, bevacizumab) Temozolomide Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15. Arm II (temozolomide, irinotecan hydrochloride, bevacizumab) Irinotecan Hydrochloride Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.
- Primary Outcome Measures
Name Time Method Overall Survival Up to 5 years after enrollment Percentage Probability of remaining alive 5 years after enrollment estimated by the method of Kaplan and Meier
- Secondary Outcome Measures
Name Time Method Event-free Survival Up to 5 years after enrollment Percentage Probability of remaining event-free 5 years after enrollment estimated by the method of Kaplan and Meier
Response Up to 12 cycles of therapy (11 months) Patient's best response during protocol therapy coded as complete response, partial response or no response.
Trial Locations
- Locations (158)
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Queensland Children's Hospital
🇦🇺South Brisbane, Queensland, Australia
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Legacy Emanuel Children's Hospital
🇺🇸Portland, Oregon, United States
Columbia Regional
🇺🇸Columbia, Missouri, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Royal Children's Hospital-Brisbane
🇦🇺Herston, Queensland, Australia
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Starship Children's Hospital
🇳🇿Grafton, Auckland, New Zealand
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Vermont and State Agricultural College
🇺🇸Burlington, Vermont, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦Montreal, Quebec, Canada
John Hunter Children's Hospital
🇦🇺Hunter Regional Mail Centre, New South Wales, Australia
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
University Pediatric Hospital
🇵🇷San Juan, Puerto Rico
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Emanuel Hospital and Health Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Nevada Cancer Research Foundation NCORP
🇺🇸Las Vegas, Nevada, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
El Paso Children's Hospital
🇺🇸El Paso, Texas, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Sydney Children's Hospital
🇦🇺Randwick, New South Wales, Australia
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
Michigan State University Clinical Center
🇺🇸East Lansing, Michigan, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
University of Rochester
🇺🇸Rochester, New York, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States