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Risk-Based Therapy in Treating Younger Patients with Newly Diagnosed Liver Cancer

Trial Status: Closed to Accrual and Intervention

This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy.

Inclusion Criteria

  • Patients must be newly diagnosed with histologically-proven hepatoblastoma
  • In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled on AHEP0731 without a biopsy * Clinical situations in which such emergent treatment may be indicated include, but are not limited to, the following circumstances: ** Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc) ** Uncorrectable coagulopathy * For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur: ** The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment ** Patient must be enrolled on AHEP0731 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment ** If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
  • Patients will be staged for risk classification and treatment at diagnosis using Children's Oncology Group (COG) staging guidelines
  • At the time of study enrollment, the patient’s treatment regimen must be identified; if the patient’s primary tumor was resected prior to the day of enrollment and a blood specimen for the determination of serum alpha fetoprotein was not obtained prior to that surgery, the patient will be considered to have alpha fetoprotein of greater than 100 ng/mL for the purpose of treatment assignment; if tumor samples obtained prior to the date of enrollment were not sufficient to determine whether small cell undifferentiated (SCU) histology was present, treatment assignment will be made assuming SCU is not present in the tumor
  • For patients with stage I or II disease, specimens for rapid central review have been submitted and the rapid central review diagnosis and staging must be available to be provided on the AHEP0731 eligibility case report form (CRF)
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients may have had surgical resection of some or all sites of hepatoblastoma prior to enrollment
  • Organ function requirements are not required for enrolled patients who are stage I, PFH and will not be receiving chemotherapy
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows: * 1 month to < 6 months: 0.4 mg/dL * 6 months to < 1 year: 0.5 mg/dL * 1 to < 2 years: 0.6 mg/dL * 2 to < 6 years: 0.8 mg/dL * 6 to < 10 years: 1 mg/dL * 10 to < 13 years: 1.2 mg/dL * 13 to < 16 years: 1.5 mg/dL (male) or 1.4 mg/dL (female) * >= 16 years: 1.7 mg/dL (male) or 1.4 mg/dL (female)
  • Total bilirubin < 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age
  • Absolute neutrophil count (ANC) > 750/uL
  • Platelet count > 75,000/uL
  • Shortening fraction >= 27% by echocardiogram
  • Ejection fraction >= 47% by radionuclide angiogram (multi gated acquisition scan [MUGA]); Note: the echocardiogram (or MUGA) may be done within 28 days prior to enrollment
  • Serum triglyceride level =< 300 mg/dL (=< 3.42 mmol/L)
  • Serum cholesterol level =< 300 mg/dL (7.75 mmol/L)
  • Random or fasting blood glucose within the upper normal limits for age; if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age
  • Normal pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); Note: for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
  • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlled
  • Prothrombin time (PT) < 1.2 x ULN
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

  • Patients with stage I or II disease who do not have specimens submitted for rapid central pathology review by day 14 after initial surgical resection
  • Patients that have been previously treated with chemotherapy for hepatoblastoma or other hepatoblastoma-directed therapy (e.g., radiation therapy, biologic agents, local therapy [embolization, radiofrequency ablation, laser]) are not eligible
  • Patients who have received any prior chemotherapy are not eligible
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anticancer agents are not eligible
  • Patients who have previously received a solid organ transplant are not eligible
  • Patients who have an uncontrolled infection are not eligible
  • Females who are pregnant or breast feeding are not eligible for this study
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Males and females of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method
  • Patients receiving corticosteroids are not eligible; patients must have been off corticosteroids for 7 days prior to start of chemotherapy
  • Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
  • Patients must not be receiving any of the following potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, azithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit juice or St. John’s wort
  • Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, warfarin and others) are not eligible
  • Patients who are currently receiving angiotensin-converting enzymes (ACE) inhibitors are not eligible
  • Patients must not have had major surgery within 6 weeks prior to enrollment on the high risk stratum; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery, liver tumor biopsy) will be eligible

Alabama

Birmingham
Children's Hospital of Alabama
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Alabama at Birmingham Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Alyssa Terry Reddy
Phone: 888-823-5923
Mobile
USA Health Strada Patient Care Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 251-665-8000

Arizona

Phoenix
Phoenix Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 602-546-0920
Tucson
Banner University Medical Center - Tucson
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 520-626-9008

Arkansas

Little Rock
Arkansas Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Arkansas for Medical Sciences
Status: CLOSED_TO_ACCRUAL
Contact: David L. Becton
Phone: 501-686-8274

California

Downey
Kaiser Permanente Downey Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 626-564-3455
Loma Linda
Loma Linda University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 909-558-3375
Long Beach
Miller Children's and Women's Hospital Long Beach
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Los Angeles
Cedars Sinai Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 310-423-8965
Children's Hospital Los Angeles
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Madera
Valley Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Oakland
Children's Hospital and Research Center at Oakland
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Kaiser Permanente-Oakland
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Orange
Children's Hospital of Orange County
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Sacramento
Sutter Medical Center Sacramento
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 415-209-2686
University of California Davis Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 916-734-3089
San Diego
Naval Medical Center -San Diego
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 619-532-8712
Rady Children's Hospital - San Diego
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
San Francisco
UCSF Medical Center-Mission Bay
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-827-3222
UCSF Medical Center-Parnassus
Status: CLOSED_TO_ACCRUAL
Contact: Robert Edward Goldsby
Phone: 877-827-3222
Santa Barbara
Santa Barbara Cottage Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 805-682-7300

Colorado

Aurora
Children's Hospital Colorado
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Connecticut

Hartford
Connecticut Children's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
New Haven
Yale University
Status: CLOSED_TO_ACCRUAL
Contact: Nina Singh Kadan-Lottick
Phone: 203-785-5702

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 302-651-6884

District of Columbia

Washington
Children's National Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
MedStar Georgetown University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 202-444-2223

Florida

Fort Lauderdale
Broward Health Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 954-355-5346
Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Lee Memorial Health System
Status: CLOSED_TO_ACCRUAL
Contact: Emad K. Salman
Phone: 877-680-0008
Gainesville
University of Florida Health Science Center - Gainesville
Status: CLOSED_TO_ACCRUAL
Contact: William Birdsall Slayton
Phone: 352-273-8675
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Miami
Miami Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 786-596-2000
Nicklaus Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
AdventHealth Orlando
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 407-303-2090
Arnold Palmer Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 321-843-2584
Nemours Children's Clinic - Orlando
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Phone: 888-823-5923
Nemours Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Orlando Health Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Vincent Ferdinando Giusti
Phone: 321-841-7246
Pensacola
Nemours Children's Clinic - Pensacola
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
West Palm Beach
Saint Mary's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Savannah
Memorial Health University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 912-350-7887

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 808-983-6090
Tripler Army Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Tonya Marie Kratovil
Phone: 808-433-6336
University of Hawaii Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Robert W. Wilkinson
Phone: 888-823-5923

Idaho

Boise
Saint Luke's Cancer Institute - Boise
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Chicago Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 708-226-4357
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Park Ridge
Advocate Children's Hospital-Park Ridge
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Advocate Lutheran General Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Rebecca Erin McFall
Phone: 888-823-5923
Peoria
Saint Jude Midwest Affiliate
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-226-4343
Springfield
Southern Illinois University School of Medicine
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 217-545-7929

Indiana

Indianapolis
Riley Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-248-1199
Saint Vincent Hospital and Health Care Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 317-338-2194

Iowa

Des Moines
Blank Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Louisiana

New Orleans
Children's Hospital New Orleans
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Ochsner Medical Center Jefferson
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 504-703-8712
Tulane University Health Sciences Center
Status: CLOSED_TO_ACCRUAL
Contact: Tammuella Chrisentery Singleton
Phone: 504-988-6121

Maine

Bangor
Eastern Maine Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 207-973-4274
Scarborough
Maine Children's Cancer Program
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Maryland

Baltimore
Sinai Hospital of Baltimore
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 410-601-6120
Bethesda
Walter Reed National Military Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 301-319-2100

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-442-3324
Massachusetts General Hospital Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-726-5130
Worcester
UMass Memorial Medical Center - University Campus
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 508-856-3216

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Detroit
Ascension Saint John Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 734-712-3671
Wayne State University / Karmanos Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 313-576-9790
East Lansing
Michigan State University Clinical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 517-975-9547
Flint
Hurley Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Nkechi Onwuzurike
Phone: 734-712-3671
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Kalamazoo
Bronson Methodist Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Kalamazoo Center for Medical Studies
Status: CLOSED_TO_ACCRUAL
Contact: Jeffrey S. Lobel
Phone: 888-823-5923

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Minnesota / Masonic Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Rochester
Mayo Clinic in Rochester
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 855-776-0015

Mississippi

Jackson
University of Mississippi Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Columbia
Columbia Regional
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Missouri - Ellis Fischel
Status: WITHDRAWN
Contact: Thomas Ward Loew
Phone: 573-882-7440
Kansas City
Children's Mercy Hospitals and Clinics
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Saint Louis
Mercy Hospital Saint Louis
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 314-251-6770
Washington University School of Medicine
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-600-3606

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Nebraska Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 402-559-6941

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Nevada Cancer Research Foundation NCORP
Status: ACTIVE
Contact: Jonathan Bernstein
Phone: 702-384-0013
Summerlin Hospital Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Sunrise Hospital and Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
University Medical Center of Southern Nevada
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-639-6918

New Jersey

Hackensack
Hackensack University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 201-996-2879
Morristown
Morristown Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 973-971-5900
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 732-235-8675
Saint Peter's University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Newark
Newark Beth Israel Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 973-926-7230
Paterson
Saint Joseph's Regional Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Summit
Overlook Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Steven Lon Halpern
Phone: 201-996-2879

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 505-925-0366

New York

Albany
Albany Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 518-262-5513
Bronx
Montefiore Medical Center - Moses Campus
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 718-379-6866
Buffalo
Roswell Park Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-767-9355
Mineola
NYU Winthrop Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 516-663-3115
New Hyde Park
The Steven and Alexandra Cohen Children's Medical Center of New York
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-263-4434
Memorial Sloan Kettering Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-639-7592
Mount Sinai Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-824-7309
Email: CCTO@mssm.edu
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-305-6361
Rochester
University of Rochester
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 585-275-5830
Syracuse
State University of New York Upstate Medical University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 315-464-5476
Valhalla
New York Medical College
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 914-594-3794

North Carolina

Asheville
Mission Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 828-213-4150
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 704-355-2884
Novant Health Presbyterian Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 704-384-5369
Durham
Duke University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-275-3853
Greenville
East Carolina University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 252-744-2391
Winston-Salem
Wake Forest University Health Sciences
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 336-713-6771

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Cleveland
Cleveland Clinic Foundation
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-223-8100
Rainbow Babies and Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Dayton
Dayton Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Toledo
Mercy Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-823-5923

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 405-271-8777

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Legacy Emanuel Hospital and Health Center
Status: CLOSED_TO_ACCRUAL
Contact: Janice Faye Olson
Phone: 503-413-8199
Oregon Health and Science University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 503-494-1080

Pennsylvania

Hershey
Penn State Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Philadelphia
Children's Hospital of Philadelphia
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Saint Christopher's Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Puerto Rico

San Juan
San Jorge Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University Pediatric Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 787-474-0333

Rhode Island

Providence
Rhode Island Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 401-444-1488

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 843-792-9321
Columbia
Prisma Health Richland Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 803-434-3680
Greenville
BI-LO Charities Children's Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Greenville Cancer Treatment Center
Status: CLOSED_TO_ACCRUAL
Contact: Cary E. Stroud
Phone: 888-823-5923

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 605-312-3320

Tennessee

Chattanooga
T C Thompson Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Manoo G. Bhakta
Knoxville
East Tennessee Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 865-541-8266
Memphis
Saint Jude Children's Research Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Nashville
The Children's Hospital at TriStar Centennial
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Vanderbilt University / Ingram Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Corpus Christi
Driscoll Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Dallas
Medical City Dallas Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 214-648-7097
El Paso
El Paso Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Fort Sam Houston
Brooke Army Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 210-916-4837
Fort Worth
Cook Children's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 713-798-1354
Lubbock
UMC Cancer Center / UMC Health System
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
San Antonio
Children's Hospital of San Antonio
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Methodist Children's Hospital of South Texas
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Texas Health Science Center at San Antonio
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 210-450-3800
Temple
Scott and White Memorial Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 254-724-5407

Utah

Salt Lake City
Primary Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Virginia

Charlottesville
University of Virginia Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 434-243-6303
Falls Church
Inova Fairfax Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 703-208-6650
Norfolk
Children's Hospital of The King's Daughters
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Roanoke
Carilion Children's
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Washington

Seattle
Seattle Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Tacoma
Madigan Army Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 253-968-0129
Mary Bridge Children's Hospital and Health Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

West Virginia

Charleston
West Virginia University Charleston Division
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-388-9944
Morgantown
West Virginia University Healthcare
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-293-7374

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: CLOSED_TO_ACCRUAL
Contact: Kenneth Brian De Santes
Phone: 800-622-8922
Milwaukee
Children's Hospital of Wisconsin
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 414-955-4727

Alberta

Calgary
Alberta Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

British Columbia

Vancouver
British Columbia Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Manitoba

Winnipeg
CancerCare Manitoba
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-561-1026

Nova Scotia

Halifax
IWK Health Centre
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 902-470-6767

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Kingston
Kingston Health Sciences Centre
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 613-549-6666
Ottawa
Children's Hospital of Eastern Ontario
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Toronto
Hospital for Sick Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 416-813-7654ext2027

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Quebec
Centre Hospitalier Universitaire de Quebec
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Saskatchewan

Saskatoon
Saskatoon Cancer Centre
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 306-655-2914

Australia

Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
North Adelaide
Women's and Children's Hospital-Adelaide
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Perth
Princess Margaret Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: (08) 9340 8222
Westmead
The Children's Hospital at Westmead
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Brazil

Sao Paulo
Instituto De Oncologia Pediatrica
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Japan

Fukushima City
Fukushima Medical University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 813 5791 6398
Hiroshima City
Hiroshima University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 82-424-6042
Itabashi-ku
Nihon University Itabashi Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 03-3972-8111
Kagoshima City
Kagoshima University Medical Dental Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 81-99-275-5111
Shizuoka City
Shizuoka Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 81-55-989-5222
Tokyo
National Cancer Center Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 81-3-3542-2511

PRIMARY OBJECTIVES:

I. To estimate the event-free survival (EFS) in children with stage I (non-pure fetal histology [PFH], non-small cell undifferentiated [SCU]) and stage II (non-SCU) hepatoblastoma treated with surgical resection followed by 2 cycles of cisplatin, fluorouracil, and vincristine sulfate (C5V).

II. To determine the feasibility and toxicity of adding doxorubicin (doxorubicin hydrochloride) to the chemotherapy regimen of C5V for children with intermediate-risk hepatoblastoma.

III. To estimate the response rate to vincristine (vincristine sulfate), irinotecan (irinotecan hydrochloride), and temsirolimus in previously untreated children with high-risk, metastatic hepatoblastoma.

IV. To determine whether timely (between diagnosis and end of second cycle of chemotherapy) consultation with a treatment center with surgical expertise in major pediatric liver resection and transplant can be achieved in 70% of patients with potentially unresectable hepatoblastoma.

V. To foster the collection of tumor tissue and biologic samples to facilitate translational research and to provide data that may aid in risk-adapted approaches for subsequent clinical trials.

SECONDARY OBJECTIVES:

I. To estimate the EFS of patients with stage I PFH treated with surgery alone.

II. To determine whether orthotopic liver transplantation (OLT) can be accomplished after successful referral and completion of 4 cycles of initial chemotherapy.

III. To estimate the 2-year EFS for patients once identified as candidates for possible OLT, the 2-year EFS for patients referred to a transplant center that are resected without OLT, and the 2-year EFS for patients referred to a transplant center who receive OLT.

IV. To register children with hepatoblastoma who receive OLT with PLUTO (Pediatric Liver Unresectable Tumor Observatory), an international cooperative registry for children transplanted for liver tumors.

V. To determine if pretreatment extent of disease (PRETEXT) grouping can predict tumor resectability.

VI. To monitor the concordance between institutional assessment of PRETEXT grouping and PRETEXT grouping as performed by expert panel review.

VII. To estimate the proportion of stage IV patients who have surgical resection of metastatic pulmonary lesions.

VIII. To determine the proportion and estimate the EFS of patients with potentially poor prognostic factors including alpha fetoprotein (AFP) < 100 ng/mL at diagnosis, microscopic positive surgical margins, surgical complications, multifocal tumors, microscopic vascular invasion, macrotrabecular histologic subtype, and SCU histologic subtype.

OUTLINE: Patients are assigned to 1 of 4 treatment groups according to risk group.

VERY LOW-RISK GROUP: Patients undergo surgery and receive no further treatment.

LOW-RISK GROUP: (regimen T) Patients undergo surgery and then receive adjuvant cisplatin intravenously (IV) over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

INTERMEDIATE-RISK GROUP: (regimen F) (closed to accrual as of 3/12/2012) Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

HIGH-RISK GROUP: (regimen W) (regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

HIGH-RISK GROUP: (regimen H) Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

After completion of study therapy, patients who receive chemotherapy are followed up periodically for at least 4 years.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Howard Mark Katzenstein

  • Primary ID AHEP0731
  • Secondary IDs NCI-2011-01975, 10-00098, COG-AHEP0731, CDR0000654889, NCT02265692
  • Clinicaltrials.gov ID NCT00980460