- 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).
- To determine the feasibility and toxicity of adding doxorubicin hydrochloride to the chemotherapy regimen of C5V for pediatric patients with intermediate-risk hepatoblastoma.
- To estimate the response rate to vincristine and irinotecan hydrochloride in previously untreated pediatric patients with high-risk, metastatic hepatoblastoma.
- 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.
- 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.
- To estimate the EFS of patients with stage I PFH treated with surgery alone.
- To determine whether liver transplantation (OLT) can be accomplished after successful referral and completion of 4 courses of initial chemotherapy.
- 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.
- 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.
- To determine if PRETEXT grouping can predict tumor resectability.
- To monitor the concordance between institutional assessment of PRETEXT grouping and PRETEXT grouping as performed by expert panel review.
- To estimate the proportion of stage IV patients who have surgical resection of metastatic pulmonary lesions.
- 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.
- Histologically confirmed newly diagnosed hepatoblastoma
- All stages* and all histologic variants allowed NOTE: *Patients with Stage I or II disease must have specimens submitted for rapid central pathology review by Day 14 after initial surgical resection
- 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 NOTE: *Organ function requirements are not required for enrolled patients who are stage I, PFH and will not be receiving chemotherapy.
NOTE: **For intermediate- and high-risk patients who will be assigned to protocol chemotherapy.
PRIOR CONCURRENT THERAPY:
- 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
Last updated: 11/22/2012
NCT ID: NCT00980460