Know Cancer

forgot password

Treatment of Children With All Stages of Hepatoblastoma

Phase 3
21 Years
Open (Enrolling)
Childhood Hepatoblastoma, Stage I Childhood Liver Cancer, Stage II Childhood Liver Cancer, Stage III Childhood Liver Cancer, Stage IV Childhood Liver Cancer

Thank you

Trial Information

Treatment of Children With All Stages of Hepatoblastoma


I. To estimate the event-free survival (EFS) in pediatric patients with stage I (non-PFH,
non-SCU) and stage II (non-SCU) hepatoblastoma treated with surgical resection followed by 2
courses of cisplatin, fluorouracil, and vincristine (C5V).

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

III. To estimate the response rate to vincristine and irinotecan hydrochloride in previously
untreated pediatric patients with high-risk, metastatic hepatoblastoma.

IV. To determine whether timely (between diagnosis and end of second course 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

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


I. To estimate the EFS of patients with stage I PFH treated with surgery alone. II. To
determine whether liver transplantation (OLT) can be accomplished after successful referral
and completion of 4 courses 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 pediatric patients with hepatoblastoma who receive OLT with PLUTO (Pediatric
Liver Unresectable Tumor Observatory), an international cooperative registry for pediatric
patients transplanted for liver tumors.

V. To determine if 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 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: This is a multicenter study. Patients are stratified according to risk (very low vs
low vs intermediate vs high). 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 IV
over 6 hours on day 1, fluorouracil IV on day 2, and vincristine sulfate IV 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) Patients receive C5VD chemotherapy comprising cisplatin
IV over 6 hours on day 1, fluorouracil IV on day 2, vincristine sulfate IV 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.

HIGH-RISK GROUP: (regimen W) 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. Patients undergo tumor resection or liver transplantation after course 4 of C5VD
followed by 2 courses of adjuvant C5VD.

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

Inclusion Criteria:

- Histologically confirmed newly diagnosed hepatoblastoma

- All stages* and all histologic variants allowed

- Patients are assigned to the following risk groups:

- Very low-risk: grossly resected tumors (stage I) with PFH AND an elevated AFP
level > 100 ng/mL

- Low-risk: grossly resected tumors (stage I-II) AND lacking any unfavorable
biologic feature (i.e., any SCU elements or a low diagnostic AFP level < 100

- Intermediate-risk: gross residual disease/unresectable disease OR grossly
resected disease with any SCU elements but no metastatic disease and no low
diagnostic AFP level < 100 ng/mL

- High-risk: metastatic disease OR low diagnostic AFP level < 100 ng/mL regardless
of stage

- ECOG performance status 0-2

- ANC* > 750/μL

- Platelet count* > 75,000/μL

- Creatinine clearance* or radioisotope glomerular filtration rate* ≥ 70 mL/min 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) 1.4 mg/dL (female)

- Total bilirubin* < 1.5 times upper limit of normal (ULN) for age

- SGOT (AST)* or SGPT (ALT)* < 10 times ULN for age

- Shortening fraction** ≥ 27% by echocardiogram

- Ejection fraction** ≥ 47% by radionuclide angiogram (MUGA)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Prior surgical resection of some or all sites of hepatoblastoma allowed

- No prior chemotherapy for hepatoblastoma or other hepatoblastoma-directed therapy
(e.g., radiation therapy, biologic agents, local therapy [embolization,
radiofrequency ablation, laser])

- No other prior chemotherapy

- No concurrent radiotherapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Outcome Description:

Estimated by the method of Kaplan and Meier.

Outcome Time Frame:

Time from patient enrollment to progression, treatment failure, death from any cause, diagnosis of a second malignant neoplasm, or last follow-up, assessed up to 5 years

Safety Issue:


Principal Investigator

Howard Katzenstein

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

Related Keywords:

  • Childhood Hepatoblastoma
  • Stage I Childhood Liver Cancer
  • Stage II Childhood Liver Cancer
  • Stage III Childhood Liver Cancer
  • Stage IV Childhood Liver Cancer
  • Liver Neoplasms
  • Hepatoblastoma



Baylor College of Medicine Houston, Texas  77030
Memorial Sloan Kettering Cancer Center New York, New York  10021
Cleveland Clinic Foundation Cleveland, Ohio  44195
Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Tripler Army Medical Center Honolulu, Hawaii  96859-5000
Hurley Medical Center Flint, Michigan  48503
Rhode Island Hospital Providence, Rhode Island  02903
Medical City Dallas Hospital Dallas, Texas  75230
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
Sinai Hospital of Baltimore Baltimore, Maryland  21225
Bronson Methodist Hospital Kalamazoo, Michigan  49007
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Loyola University Medical Center Maywood, Illinois  60153
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Morristown Memorial Hospital Morristown, New Jersey  07962-1956
Loma Linda University Medical Center Loma Linda, California  92354
Baptist Hospital of Miami Miami, Florida  33176-2197
Newark Beth Israel Medical Center Newark, New Jersey  07112
New York Medical College Valhalla, New York  10595
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Cedars-Sinai Medical Center Los Angeles, California  90048
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Brooke Army Medical Center Fort Sam Houston, Texas  78234-6200
Madigan Army Medical Center Tacoma, Washington  98431-5048
Eastern Maine Medical Center Bangor, Maine  04401
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Hackensack University Medical Center Hackensack, New Jersey  07601
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's National Medical Center Washington, District of Columbia  20010-2970
All Children's Hospital St. Petersburg, Florida  33701
Advocate Hope Children's Hospital Oak Lawn, Illinois  60453
Saint Jude Midwest Affiliate Peoria, Illinois  61637
Ochsner Clinic Foundation New Orleans, Louisiana  70121
Maine Children's Cancer Program Scarborough, Maine  04074-9308
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health Center Portland, Oregon  97227
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Driscoll Children's Hospital Corpus Christi, Texas  78466
Scott and White Memorial Hospital Temple, Texas  76508
Inova Fairfax Hospital Falls Church, Virginia  22042-3300
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Children's Hospital Medical Center of Akron Akron, Ohio  44308
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Overlook Hospital Summit, New Jersey  07902-0220
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Methodist Children's Hospital of South Texas San Antonio, Texas  78229-3993
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
Montefiore Medical Center Bronx, New York  10467-2490
Saint Peter's University Hospital New Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San Diego San Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central Texas Austin, Texas  78723
Children's Hospital and Research Center at Oakland Oakland, California  94609-1809
Mary Bridge Children's Hospital and Health Center Tacoma, Washington  98415-0299
Presbyterian Hospital Charlotte, North Carolina  28233-3549
Lee Memorial Health System Fort Myers, Florida  33902
University of Virginia Charlottesville, Virginia  22908
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Children's Hospital of Alabama Birmingham, Alabama  35233
Connecticut Children's Medical Center Hartford, Connecticut  06106
University of North Carolina Chapel Hill, North Carolina  27599
Duke University Medical Center Durham, North Carolina  27710
University of Florida Gainesville, Florida  32610-0277
University of Rochester Rochester, New York  14642
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum Health Grand Rapids, Michigan  49503
Yale University New Haven, Connecticut  06520
Wayne State University Detroit, Michigan  48202
Mercy Children's Hospital Toledo, Ohio  43608
Legacy Emanuel Children's Hospital Portland, Oregon  97227
BI-LO Charities Children's Cancer Center Greenville, South Carolina  29605
University of Arizona Health Sciences Center Tucson, Arizona  85724
University of Massachusetts Medical School Worcester, Massachusetts  01605
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
Albany Medical Center Albany, New York  12208
University of Texas Southwestern Medical Center Dallas, Texas  
University of Kentucky Lexington, Kentucky  40536-0098
Oregon Health and Science University Portland, Oregon  97201
Tulane University Health Sciences Center New Orleans, Louisiana  70112
Virginia Commonwealth University Richmond, Virginia  
Florida Hospital Orlando, Florida  32803
Memorial Health University Medical Center Savannah, Georgia  31404
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Seattle Children's Hospital Seattle, Washington  98105
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
Childrens Memorial Hospital Chicago, Illinois  60614
Kaiser Permanente-Oakland Oakland, California  94611
Lombardi Comprehensive Cancer Center at Georgetown University Washington, District of Columbia  20057
M D Anderson Cancer Center- Orlando Orlando, Florida  32806
University of Hawaii Honolulu, Hawaii  96813
Saint Luke's Mountain States Tumor Institute Boise, Idaho  83712
Saint Vincent Hospital and Health Services Indianapolis, Indiana  46260
Michigan State University - Breslin Cancer Center East Lansing, Michigan  48824-1313
Kalamazoo Center for Medical Studies Kalamazoo, Michigan  49008
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
New York University Langone Medical Center New York, New York  10016
Columbia University Medical Center New York, New York  10032
State University of New York Upstate Medical University Syracuse, New York  13210
Mission Hospitals Inc Asheville, North Carolina  28801
Cook Children's Medical Center Fort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's Hospital Hollywood, Florida  33021
West Virginia University Charleston Charleston, West Virginia  25304
The Children's Medical Center of Dayton Dayton, Ohio  45404
Advocate Lutheran General Hospital Park Ridge, Illinois  60068
University of Miami Miller School of Medicine-Sylvester Cancer Center Miami, Florida  33136
University of Minnesota Medical Center-Fairview Minneapolis, Minnesota  55455
C S Mott Children's Hospital Ann Arbor, Michigan  48109
Southern Illinois University Springfield, Illinois  62702
University Of Missouri-Columbia Columbia, Missouri  65212
Walter Reed National Military Medical Center Bethesda, Maryland  20889
Riley Hospital for Children Indianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
Phoenix Childrens Hospital Phoenix, Arizona  85016
Miller Children's Hospital Long Beach, California  90806
Childrens Hospital of Orange County Orange, California  92868-3874
Alfred I duPont Hospital for Children Wilmington, Delaware  19803
Nemours Children's Clinic - Jacksonville Jacksonville, Florida  32207-8426
Nemours Childrens Clinic - Orlando Orlando, Florida  32806
Saint Joseph Children's Hospital of Tampa Tampa, Florida  33607
Children's Healthcare of Atlanta - Egleston Atlanta, Georgia  30322
The Childrens Mercy Hospital Kansas City, Missouri  64108
Rainbow Babies and Childrens Hospital Cleveland, Ohio  44106
Penn State Hershey Children's Hospital Hershey, Pennsylvania  17033
Palmetto Health Richland Columbia, South Carolina  29203
East Tennessee Childrens Hospital Knoxville, Tennessee  37916
Children's Hospital and Medical Center of Omaha Omaha, Nebraska  68114
Saint Joseph's Regional Medical Center Paterson, New Jersey  07503
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
Children's Hospital Colorado Aurora, Colorado  80045
Lucile Packard Children's Hospital Stanford University Palo Alto, California  94304
University of California San Francisco Medical Center-Parnassus San Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver, Colorado  80218
Raymond Blank Children's Hospital Des Moines, Iowa  50309
Children's Hospital-Main Campus New Orleans, Louisiana  70118
Saint Christopher's Hospital for Children Philadelphia, Pennsylvania  19134
Greenville Cancer Treatment Center Greenville, South Carolina  29605
T C Thompson Children's Hospital Chattanooga, Tennessee  37403
Carilion Clinic Children's Hospital Roanoke, Virginia  24014
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204
Broward Health Medical Center Fort Lauderdale, Florida  33316
The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park, New York  11040