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

NCT ID: NCT00980460

Last Updated: 2025-11-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

236 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-14

Study Completion Date

2026-03-19

Brief Summary

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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.

Detailed Description

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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.

Conditions

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PRETEXT I Hepatoblastoma PRETEXT II Hepatoblastoma PRETEXT III Hepatoblastoma PRETEXT IV Hepatoblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Liver Transplantation

Intervention Type PROCEDURE

Undergo liver transplant

Temsirolimus

Intervention Type DRUG

Given IV

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Vincristine Sulfate

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Vincristine Sulfate

Intervention Type DRUG

Given IV

Intermediate-risk group (regimen F)

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. (Closed to accrual as of 3/12/2012)

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Given IV

Dexrazoxane

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Liver Transplantation

Intervention Type PROCEDURE

Undergo liver transplant

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Vincristine Sulfate

Intervention Type DRUG

Given IV

Low-risk group (regimen T)

Patients undergo surgery and then receive adjuvant cisplatin 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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Vincristine Sulfate

Intervention Type DRUG

Given IV

Very low-risk group

Patients undergo surgery and then receive no further treatment.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Interventions

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Cisplatin

Given IV

Intervention Type DRUG

Dexrazoxane

Given IV

Intervention Type DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Irinotecan Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Liver Transplantation

Undergo liver transplant

Intervention Type PROCEDURE

Temsirolimus

Given IV

Intervention Type DRUG

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Vincristine Sulfate

Given IV

Intervention Type DRUG

Other Intervention Names

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Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin 2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI) 2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI) ADR 529 ADR-529 ADR529 ICRF 187 ICRF-187 ICRF187 Razoxane (+)-form Soluble ICRF (L-isomer) 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin HCl Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 FI106 hydroxydaunorubicin Rubex 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 CPT11 Irinomedac Irinotecan Hydrochloride Trihydrate Irinotecan Monohydrochloride Trihydrate U 101440E U-101440E U101440E Hepatic Transplantation Liver Grafting Liver Transplant Transplantation of Liver CCI 779 CCI-779 CCI-779 Rapamycin Analog CCI779 Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Eligibility Criteria

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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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Howard M Katzenstein

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Site Status

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Sutter Medical Center Sacramento

Sacramento, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

Naval Medical Center -San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Santa Barbara Cottage Hospital

Santa Barbara, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Site Status

Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Site Status

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Saint Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Tripler Army Medical Center

Honolulu, Hawaii, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, United States

Site Status

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Norton Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Maine Children's Cancer Program

Scarborough, Maine, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Health Saint John Hospital

Detroit, Michigan, United States

Site Status

Michigan State University

East Lansing, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

Kalamazoo Center for Medical Studies

Kalamazoo, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Missouri Children's Hospital

Columbia, Missouri, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Research Foundation NCORP

Las Vegas, Nevada, United States

Site Status

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Site Status

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Saint Peter's University Hospital

New Brunswick, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

Overlook Hospital

Summit, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU Langone Hospital - Long Island

Mineola, New York, United States

Site Status

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

Mount Sinai Hospital

New York, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

Mercy Children's Hospital

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Site Status

Legacy Emanuel Hospital and Health Center

Portland, Oregon, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Prisma Health Richland Hospital

Columbia, South Carolina, United States

Site Status

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Site Status

Greenville Cancer Treatment Center

Greenville, South Carolina, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

El Paso Children's Hospital

El Paso, Texas, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

UMC Cancer Center / UMC Health System

Lubbock, Texas, United States

Site Status

Children's Hospital of San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Scott and White Memorial Hospital

Temple, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Site Status

Carilion Children's

Roanoke, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

West Virginia University Charleston Division

Charleston, West Virginia, United States

Site Status

West Virginia University Healthcare

Morgantown, West Virginia, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

John Hunter Children's Hospital

Hunter Regional Mail Centre, New South Wales, Australia

Site Status

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Site Status

Women's and Children's Hospital-Adelaide

North Adelaide, South Australia, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Instituto De Oncologia Pediatrica

São Paulo, , Brazil

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Site Status

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, , Canada

Site Status

Fukushima Medical University Hospital

Fukushima, Fukushima, Japan

Site Status

Kagoshima University Medical Dental Hospital

Kagoshima, Kagoshima-ken, Japan

Site Status

Shizuoka Cancer Center

Shizuoka, Suntou, Japan

Site Status

Nihon University Itabashi Hospital

Itabashi-ku, Tokyo, Japan

Site Status

Hiroshima University Hospital

Hiroshima, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

San Jorge Children's Hospital

San Juan, , Puerto Rico

Site Status

University Pediatric Hospital

San Juan, , Puerto Rico

Site Status

Countries

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United States Australia Brazil Canada Japan Puerto Rico

References

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Thompson PA, Malogolowkin MH, Furman WL, Piao J, Krailo MD, Chung N, Brock L, Towbin AJ, McCarville EB, Finegold MJ, Ranganathan S, Dunn SP, Langham MR, McGahren ED, Tiao GM, Weldon CB, O'Neill AF, Rodriguez-Galindo C, Meyers RL, Katzenstein HM. Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee. Pediatr Blood Cancer. 2023 Jul;70(7):e30365. doi: 10.1002/pbc.30365. Epub 2023 Apr 19.

Reference Type DERIVED
PMID: 37073741 (View on PubMed)

Trobaugh-Lotrario A, Katzenstein HM, Ranganathan S, Lopez-Terrada D, Krailo MD, Piao J, Chung N, Randazzo J, Malogolowkin MH, Furman WL, McCarville EB, Towbin AJ, Tiao GM, Dunn SP, Langham MR, McGahren ED, Feusner J, Rodriguez-Galindo C, Meyers RL, O'Neill AF, Finegold MJ. Small Cell Undifferentiated Histology Does Not Adversely Affect Outcome in Hepatoblastoma: A Report From the Children's Oncology Group (COG) AHEP0731 Study Committee. J Clin Oncol. 2022 Feb 10;40(5):459-467. doi: 10.1200/JCO.21.00803. Epub 2021 Dec 7.

Reference Type DERIVED
PMID: 34874751 (View on PubMed)

Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):719-727. doi: 10.1016/S1470-2045(18)30895-7. Epub 2019 Apr 8.

Reference Type DERIVED
PMID: 30975630 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Other Identifiers

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NCI-2011-01975

Identifier Type: REGISTRY

Identifier Source: secondary_id

AHEP0731

Identifier Type: -

Identifier Source: secondary_id

10-00098

Identifier Type: -

Identifier Source: secondary_id

COG-AHEP0731

Identifier Type: -

Identifier Source: secondary_id

CDR0000654889

Identifier Type: -

Identifier Source: secondary_id

AHEP0731

Identifier Type: OTHER

Identifier Source: secondary_id

AHEP0731

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01975

Identifier Type: -

Identifier Source: org_study_id

NCT02265692

Identifier Type: -

Identifier Source: nct_alias

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