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

Inclusion Criteria:

• Patients must be newly diagnosed with histologically-proven hepatoblastoma

• In emergency situations when a patient meets all other eligibility criteria and hashad baseline required observations, but is too ill to undergo a biopsy safely, thepatient 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 isgiven, the following must occur:

• The patient must have a clinical diagnosis of hepatoblastoma, including anelevated alpha fetoprotein, and must meet all AHEP0731 eligibilitycriteria 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 toAHEP0731 enrollment

• If the patient receives AHEP0731 chemotherapy PRIOR to undergoing adiagnostic biopsy, pathologic review of material obtained in the futureduring either biopsy or surgical resection must either confirm thediagnosis of hepatoblastoma or not reveal another pathological diagnosisto be included in the analysis of the study aims

• Patients will be staged for risk classification and treatment at diagnosis usingChildren'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 ablood specimen for the determination of serum alpha fetoprotein was not obtainedprior to that surgery, the patient will be considered to have alpha fetoprotein ofgreater than 100 ng/mL for the purpose of treatment assignment; if tumor samplesobtained prior to the date of enrollment were not sufficient to determine whethersmall cell undifferentiated (SCU) histology was present, treatment assignment willbe made assuming SCU is not present in the tumor

• For patients with stage I or II disease, specimens for rapid central review havebeen submitted and the rapid central review diagnosis and staging must be availableto be provided on the AHEP0731 eligibility case report form (CRF)

• Patients must have a performance status corresponding to Eastern CooperativeOncology Group (ECOG) scores 0, 1, or 2; use Karnofsky for patients > 16 years ofage and Lansky for patients =< 16 years of age

• Patients may have had surgical resection of some or all sites of hepatoblastomaprior 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) >= 70mL/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]) orserum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 xULN 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 toenrollment

• 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 theinitial blood glucose is a random sample that is outside of the normal limits, thena follow-up fasting blood glucose can be obtained and must be within the uppernormal limits for age

• Normal pulmonary function tests (including diffusing capacity of the lungs forcarbon monoxide [DLCO]) if there is clinical indication for determination (e.g.dyspnea at rest, known requirement for supplemental oxygen); Note: for patients whodo not have respiratory symptoms or requirement for supplemental oxygen, pulmonaryfunction tests (PFTs) are NOT required

• Patients with seizure disorder may be enrolled if on non-enzyme inducinganticonvulsants 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 informedconsent

• 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 rapidcentral pathology review by day 14 after initial surgical resection

• Patients that have been previously treated with chemotherapy for hepatoblastoma orother 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 negativepregnancy test result has been obtained

• Males and females of reproductive potential are not eligible unless they have agreedto use an effective contraceptive method

• Patients receiving corticosteroids are not eligible; patients must have been offcorticosteroids for 7 days prior to start of chemotherapy

• Patients who are currently receiving enzyme inducing anticonvulsants are noteligible

• 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) inhibitorsare not eligible

• Patients must not have had major surgery within 6 weeks prior to enrollment on thehigh risk stratum; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery, livertumor biopsy) will be eligible