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Treatment of Children With All Stages of Hepatoblastoma


Phase 3
N/A
21 Years
Open (Enrolling)
Both
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


PRIMARY OBJECTIVES:

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
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 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
ng/mL)

- 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:

Interventional

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:

No

Principal Investigator

Howard Katzenstein

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

AHEP0731

NCT ID:

NCT00980460

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

Name

Location

Baylor College of MedicineHouston, Texas  77030
Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Cleveland Clinic FoundationCleveland, Ohio  44195
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Tripler Army Medical CenterHonolulu, Hawaii  96859-5000
Hurley Medical CenterFlint, Michigan  48503
Rhode Island HospitalProvidence, Rhode Island  02903
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Bronson Methodist HospitalKalamazoo, Michigan  49007
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Loyola University Medical CenterMaywood, Illinois  60153
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Loma Linda University Medical CenterLoma Linda, California  92354
Baptist Hospital of MiamiMiami, Florida  33176-2197
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Cedars-Sinai Medical CenterLos Angeles, California  90048
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Brooke Army Medical CenterFort Sam Houston, Texas  78234-6200
Madigan Army Medical CenterTacoma, Washington  98431-5048
Eastern Maine Medical CenterBangor, Maine  04401
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
All Children's HospitalSt. Petersburg, Florida  33701
Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health CenterPortland, Oregon  97227
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Driscoll Children's HospitalCorpus Christi, Texas  78466
Scott and White Memorial HospitalTemple, Texas  76508
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital Medical Center of AkronAkron, Ohio  44308
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Overlook HospitalSummit, New Jersey  07902-0220
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Montefiore Medical CenterBronx, New York  10467-2490
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central TexasAustin, Texas  78723
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Lee Memorial Health SystemFort Myers, Florida  33902
University of VirginiaCharlottesville, Virginia  22908
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Children's Hospital of AlabamaBirmingham, Alabama  35233
Connecticut Children's Medical CenterHartford, Connecticut  06106
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
University of FloridaGainesville, Florida  32610-0277
University of RochesterRochester, New York  14642
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Yale UniversityNew Haven, Connecticut  06520
Wayne State UniversityDetroit, Michigan  48202
Mercy Children's HospitalToledo, Ohio  43608
Legacy Emanuel Children's HospitalPortland, Oregon  97227
BI-LO Charities Children's Cancer CenterGreenville, South Carolina  29605
University of Arizona Health Sciences CenterTucson, Arizona  85724
University of Massachusetts Medical SchoolWorcester, Massachusetts  01605
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
Albany Medical CenterAlbany, New York  12208
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
Oregon Health and Science UniversityPortland, Oregon  97201
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
Virginia Commonwealth UniversityRichmond, Virginia  
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Seattle Children's HospitalSeattle, Washington  98105
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Childrens Memorial HospitalChicago, Illinois  60614
Kaiser Permanente-OaklandOakland, California  94611
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
University of HawaiiHonolulu, Hawaii  96813
Saint Luke's Mountain States Tumor InstituteBoise, Idaho  83712
Saint Vincent Hospital and Health ServicesIndianapolis, Indiana  46260
Michigan State University - Breslin Cancer CenterEast Lansing, Michigan  48824-1313
Kalamazoo Center for Medical StudiesKalamazoo, Michigan  49008
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Cook Children's Medical CenterFort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's HospitalHollywood, Florida  33021
West Virginia University CharlestonCharleston, West Virginia  25304
The Children's Medical Center of DaytonDayton, Ohio  45404
Advocate Lutheran General HospitalPark Ridge, Illinois  60068
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
University Of Missouri-ColumbiaColumbia, Missouri  65212
Walter Reed National Military Medical CenterBethesda, Maryland  20889
Riley Hospital for ChildrenIndianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Phoenix Childrens HospitalPhoenix, Arizona  85016
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
East Tennessee Childrens HospitalKnoxville, Tennessee  37916
Children's Hospital and Medical Center of OmahaOmaha, Nebraska  68114
Saint Joseph's Regional Medical CenterPaterson, New Jersey  07503
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Children's Hospital ColoradoAurora, Colorado  80045
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterDenver, Colorado  80218
Raymond Blank Children's HospitalDes Moines, Iowa  50309
Children's Hospital-Main CampusNew Orleans, Louisiana  70118
Saint Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
T C Thompson Children's HospitalChattanooga, Tennessee  37403
Carilion Clinic Children's HospitalRoanoke, Virginia  24014
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204
Broward Health Medical CenterFort Lauderdale, Florida  33316
The Steven and Alexandra Cohen Children's Medical Center of New YorkNew Hyde Park, New York  11040