Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma



Status:Completed
Conditions:Cancer, Brain Cancer, Neurology
Therapuetic Areas:Neurology, Oncology
Healthy:No
Age Range:1 - 30
Updated:12/13/2018
Start Date:June 18, 2012
End Date:April 1, 2014

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A Phase II Study of Cixutumumab (IMC-A12) in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors

This phase II trial studies how well cixutumumab and temsirolimus work in treating patients
with recurrent or refractory sarcoma. Monoclonal antibodies, such as cixutumumab, 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.
Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. Giving cixutumumab and temsirolimus together may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the objective response rate to the combination of cixutumumab and
temsirolimus in patients with relapsed or refractory osteosarcoma, Ewing sarcoma,
rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma.

II. To further describe the toxicities (including dose-limiting toxicities) of cixutumumab
and temsirolimus administered on this schedule.

SECONDARY OBJECTIVES:

I. To assess the progression-free survival for patients treated in each disease stratum with
this drug combination.

II. To assess the incidence of insulin-like growth factor 1 receptor (IGF-1R), insulin
receptor, ERK, RON, and mammalian target of rapamycin (mTOR) pathway activation in archival
tumor material, and correlate with response.

III. To evaluate minimal residual disease and IGF-1R tumor cell expression in the blood and
bone marrow of Ewing sarcoma patients using flow cytometry.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis
(osteosarcoma vs Ewing sarcoma/PNET vs rhabdomyosarcoma vs non-rhabdomyosarcoma soft tissue
sarcoma).

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8,
15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease
progression or unacceptable toxicity.

Archived tumor tissue samples from most recent biopsy are collected and analyzed for IGF-1R,
insulin receptor, AKT, ERK, mTOR, and S6 kinase pathway activation by immunohistochemistry
(IHC) and banked for future correlative studies. Blood and bone marrow samples, from patients
with Ewing sarcoma, may be collected at baseline and periodically during treatment for
minimal residual disease analysis by flow cytometry.

After completion of study treatment, patients are followed up periodically for 5 years.

Inclusion Criteria:

- Patients with any of the following tumors who have experienced relapse following
front-line therapy, or who are refractory to front-line therapy, are eligible:

- Osteosarcoma

- Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)

- Rhabdomyosarcoma

- Non-rhabdomyosarcoma soft tissue sarcoma

- Patients must have had histologic verification of malignancy at original diagnosis or
relapse

- All patients are required to submit archival tumor samples for immunohistochemical
analysis (either paraffin-embedded tumor blocks or unstained slides)

- Tissue samples collected at original diagnosis or at relapse or at any subsequent
resections or biopsies should be available and ready for shipment to the
Biopathology Center (BPC) at time of study enrollment; the samples are required
even if tissue samples have previously been sent to the BPC for other purposes or
studies; blocks or slides should be shipped to the BPC within 7 days of study
enrollment

- Patients must have radiographically measurable disease

- Measurable disease is defined as the presence of at least one lesion on magnetic
resonance imaging (MRI) or computed tomography (CT) scan that can be accurately
measured with the longest diameter a minimum of 10 mm in at least one dimension
(CT scan slice thickness no greater than 5 mm)

- The following do not qualify as measurable disease:

- Malignant fluid collections (e.g., ascites, pleural effusions)

- Bone marrow infiltration

- Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or
positron emission tomography [PET] scans)

- Elevated tumor markers in plasma or cerebrospinal fluid(CSF)

- Previously radiated lesions that have not demonstrated clear progression
post radiation

- Leptomeningeal lesions that do not meet the measurements noted above

- Patient?s current disease state must be one for which there is no known curative
therapy or therapy proven to prolong survival with an acceptable quality of life

- Patients with known central nervous system metastases are excluded unless treated
surgically or with radiotherapy and stable with no recurrent lesions for at least 3
months

- Patients must have a Lansky or Karnofsky performance status score of ? 50%,
corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1, or 2; use
Karnofsky for patients > 16 years of age and Lansky for patients ? 16 years of age

- Patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score

- For patients with solid tumors without bone marrow involvement:

- Peripheral absolute neutrophil count (ANC) ? 1,000/?L

- Platelet count ? 100,000/?L (transfusion independent, defined as not receiving
platelet transfusions within a 7-day period prior to enrollment)

- Hemoglobin ? 8.0 g/dL (may receive red blood cell [RBC] transfusions)

- For patients with solid tumors and known bone marrow metastatic disease:

- ANC ? 750/?L

- Platelet count ? 50,000/?L (may receive platelet transfusions)

- Hemoglobin ? 8.0 g/dL (may receive RBC transfusions)

- For patients with known bone marrow metastatic disease, transfusions are
permitted to meet both platelet and hemoglobin criteria; patients must not
be known to be refractory to red blood cell or platelet transfusions

- Creatinine clearance or radioisotope GFR ? 70 mL/min OR a serum creatinine based on
age/gender as follows:

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to < 16 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) ( ? 16 years of age)

- Total bilirubin ? 1.5 times upper limit of normal (ULN)

- Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransaminase [ALT]) ? 2.5
times ULN (for the purpose of this study, the ULN for SGPT is 45 U/L)

- Serum albumin ? 2 g/dL

- Patients with seizure disorder may be enrolled if receiving non-enzyme-inducing
anticonvulsants and well controlled

- Patients with known type I or type II diabetes mellitus are not eligible

- Serum glucose values must be within the normal limits for age; if the initial blood
glucose is a random sample that is outside normal limits, then a follow-up fasting
blood glucose should be obtained and must be within the normal limits for age

- Serum cholesterol levels must be < grade 2 (< 300 mg/dL), and serum triglyceride
levels must be < grade 2 (< 2.5 times ULN)

- Patients who are pregnant or breast-feeding are not eligible for this study

- Negative pregnancy tests must be obtained in girls who are post-menarchal

- Males or females of reproductive potential may not participate unless they have agreed
to use an effective contraceptive method for the duration of the study and for 3
months after the last dose of cixutumumab

- Patients who have an uncontrolled infection are not eligible

- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study are not eligible

- See Disease Characteristics

- There is no limit to the number of prior treatment regimens; however, patients must
have fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to study enrollment

- Patients must not have received myelosuppressive chemotherapy within 3 weeks of
enrollment (6 weeks if prior nitrosourea)

- At least 7 days must have elapsed since the completion of therapy with a growth
factor; at least 14 days must have elapsed after receiving pegfilgrastim

- At least 7 days must have elapsed since the completion of therapy with a biologic
agent; for agents that have known adverse events occurring beyond 7 days after
administration, this period prior to enrollment must be extended beyond the time
during which adverse events are known to occur

- At least 3 half-lives must have elapsed since prior therapy that included a monoclonal
antibody

- ? 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); 3
months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if
therapeutic doses of metaiodobenzylguanidine(MIBG) or other substantial bone marrow
irradiation was given

- No evidence of active graft-vs-host disease and 2 months must have elapsed since stem
cell transplant or rescue

- Growth factors that support platelet or white cell number or function must not have
been administered within the 7 days prior to enrollment (14 days if Neulasta?)

- Patients receiving corticosteroids who have not been on a stable or decreasing dose of
corticosteroid for the 7 days prior to enrollment are not eligible

- Patients who are currently receiving another investigational drug are not eligible

- Patients who are currently receiving other anti-cancer agents, including chemotherapy,
radiotherapy, immunotherapy, or biologic therapy, are not eligible

- Patients receiving insulin or growth hormone therapy are not eligible

- Patients who are receiving enzyme-inducing anticonvulsants are not eligible

- Use of warfarin is not allowed while on study; patients already on warfarin should use
alternative anticoagulants while on this study; warfarin must not have been
administered within 7 days of starting protocol therapy

- Patients who have received prior therapy targeting IGF-1R with either monoclonal
antibodies or small molecule tyrosine kinase inhibitors are NOT eligible

- Prior treatment with mTOR inhibitors (e.g., rapamycin, temsirolimus, everolimus,
deforolimus) is NOT allowed

- Patients who have had major surgery within 3 weeks prior to enrollment are not
eligible; procedures such as placement of a central vascular catheter or limited tumor
biopsy are not considered major surgery
We found this trial at
75
sites
1201 Camino de Salud Northeast
Albuquerque, New Mexico 87131
(505) 272-4946
University of New Mexico Cancer Center It’s been 40 years since the New Mexico State...
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1600 7th Avenue
Birmingham, Alabama 35233
(205) 638-9100
Children's Hospital of Alabama Children
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Birmingham, AL
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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700 Childrens Drive
Columbus, Ohio 43205
(616) 722-2000
Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
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Columbus, OH
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9981 S Healthpark Dr # 465
Fort Myers, Florida 33908
239-343-5000
Lee Memorial Health System Our origins can be traced to the Fall of 1916 when...
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Fort Myers, FL
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282 Washington St
Hartford, Connecticut 06106
(860) 545-9000
Connecticut Children's Medical Center Connecticut Children’s Medical Center is a nationally recognized, 187-bed not-for-profit children’s...
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2500 N State St
Jackson, Mississippi 39216
(601) 984-1000
University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
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2401 Gillham Rd
Kansas City, Missouri 64108
(816) 234-3000
Children's Mercy Hospital Children's Mercy Hospitals and Clinics continues redefining pediatric medicine throughout the Midwest...
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529 West Markham Street
Little Rock, Arkansas 72205
(501) 686-7000
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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747 52nd St
Oakland, California 94609
(510) 428-3000
Children's Hospital and Research Center Oakland For nearly 100 years, Children's Hospital & Research Center...
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1201 W La Veta Ave
Orange, California 92868
(714) 997-3000
Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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1717 South Orange Avenue # 100
Orlando, Florida 32806
(407) 650-7000
Nemours Children's Clinic - Orlando Located near downtown Orlando, Nemours Children’s Clinic, Orlando is a...
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5153 North 9th Avenue
Pensacola, Florida 32504
(850) 505-4700
Nemours Children's Clinic - Pensacola Nemours Children’s Clinic, Pensacola serves children and families in northwest...
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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401 College Street
Richmond, Virginia 23298
(804) 828-0450
Virginia Commonwealth University Massey Cancer Center Founded in 1974, VCU Massey Cancer Center is a...
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1600 Rockland Road
Wilmington, Delaware 19803
(302) 651-4200
Alfred I. duPont Hospital for Children Nemours began more than 70 years ago with the...
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Akron, OH
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2401 W Belvedere Ave
Baltimore, Maryland 21215
(410) 601-9000
Sinai Hospital of Baltimore Sinai Hospital of Baltimore provides a broad array of high-quality, cost-effective...
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55 Fruit St
Boston, Massachusetts 02114
(617) 724-4000
Massachusetts General Hospital Cancer Center An integral part of one of the world
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Chapel Hill, North Carolina 27599
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Charlotte, North Carolina 28204
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Charlotte, North Carolina 28204
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5841 S Maryland Ave
Chicago, Illinois 60637
1-773-702-6180
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
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5 Richland Medical Park Dr
Columbia, South Carolina 29203
(803) 434-7000
Palmetto Health Richland Palmetto Health Richland, originally founded in 1892 as Columbia Hospital, has a...
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4160 John R St #2122
Detroit, Michigan 48201
(313) 833-1785
Wayne State University/Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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801 7th Avenue
Fort Worth, Texas 76104
(682) 885-4000
Cook Children's Medical Center Cook Children's Health Care System is a not-for-profit, nationally recognized pediatric...
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900 West Faris Rd.
Greenville, South Carolina 29605
(864)455-8898
BI-LO Charities Children's Cancer Center The BI-LO Charities Children
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30 Prospect Ave
Hackensack, New Jersey 07601
(201) 996-2000
Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
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Honolulu, Hawaii 96813
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Houston, Texas 77030
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705 Riley Hospital Dr
Indianapolis, Indiana 46202
(317) 944-5000
Riley Hospital for Children Riley Hospital for Children at IU Health is a place of...
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Indianapolis, Indiana 46260
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Jacksonville, Florida 32207
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2018 W Clinch Ave
Knoxville, Tennessee 37916
(865) 541-8000
East Tennessee Children's Hospital East Tennessee Children's Hospital is a not-for-profit, private, independent pediatric medical...
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Lexington, KY
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11234 Anderson St
Loma Linda, California 92354
(909) 558-4000
Loma Linda University Medical Center An outgrowth of the original Sanitarium on the hill in...
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Marshfield, Wisconsin 54449
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Miami, Florida 33155
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9000 W Wisconsin Ave #270
Milwaukee, Wisconsin 53226
(414) 266-2000
Children's Hospital of Wisconsin Nothing matters more than our children. At Children's Hospital of Wisconsin,...
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Minneapolis, Minnesota 55455
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Morristown, New Jersey 07962
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Nashville, Tennessee 37232
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New Haven, Connecticut 6520
(203) 432-4771
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
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New Orleans, Louisiana 70121
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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940 NE 13th St
Oklahoma City, Oklahoma 73190
(405) 271-6458
University of Oklahoma Health Sciences Center The OU Health Sciences Center is composed of seven...
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8200 Dodge St
Omaha, Nebraska 68114
(402) 955-5400
Children's Hospital and Medical Center of Omaha Children's Hospital & Medical Center has a rich...
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Orlando, Florida 32803
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725 Welch Rd
Palo Alto, California 94304
(650) 497-8000
Lucile Packard Children's Hospital Stanford University Stanford Children's Health is the only network in the...
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2801 N Gantenbein Ave
Portland, Oregon 97227
(503) 276-6500
Legacy Emanuel Children's Hospital For generations our children's hospital has provided outstanding care for kids...
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Rochester, Minnesota 55905
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Saint Louis, Missouri 63141
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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Saint Petersburg, Florida 33701
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San Francisco, California 94143
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Savannah, Georgia 31404
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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101 W 8th Ave
Spokane, Washington 99204
(509) 474-3131
Providence Sacred Heart Medical Center & Children's Hospital When Mother Joseph and the Sisters of...
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101 Nicolls Rd
Stony Brook, New York 11794
(631) 444-4000
Stony Brook University Medical Center Stony Brook Medicine expresses our shared mission of research, clinical...
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99 Beauvoir Avenue
Summit, New Jersey 07902
(908) 522-2000
Overlook Hospital Atlantic Health System
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311 Martin Luther King Jr Way
Tacoma, Washington 98403
(253) 403-1400
Mary Bridge Children's Hospital and Health Center Mary Bridge Children's Hospital was established in 1955,...
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2401 S. 31st Street
Temple, Texas 76508
254-724-2111
Scott & White Memorial Hospital When Arthur C. Scott, MD, and Raleigh R. White Jr.,...
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2213 Cherry Street
Toledo, Ohio 43608
(419) 251-8000
Mercy Children's Hospital Mercy Children's Hospital is a regional resource for advanced pediatric care located...
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111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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