Clinical Trials (PDQ®)
|Phase III||Tissue collection/Repository, Treatment||Active||21 and under||NCI, Other||AHEP0731|
NCI-2011-01975, CDR0000654889, COG-AHEP0731, U10CA098543, NCT00980460
This phase III trial is studying the side effects of giving doxorubicin hydrochloride together with combination chemotherapy and to compare different chemotherapy regimens to see how well they work in treating young patients with newly diagnosed liver cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether surgery is more effective with or without chemotherapy or which chemotherapy regimen may be more effective in treating young patients with liver cancer.
Further Study Information
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.
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.
- 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
Trial Lead Organizations/Sponsors
Children's Oncology GroupNational Cancer Institute
|Howard Katzenstein||Principal Investigator|
|Saint Peter's University Hospital|
|Stanley Calderwood||Ph: 732-745-8600ext6163|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00980460
ClinicalTrials.gov processed this data on September 18, 2014
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