Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Liver Cancer

This study is currently recruiting participants.
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00980460
First received: September 18, 2009
Last updated: February 5, 2014
Last verified: February 2014

September 18, 2009
February 5, 2014
September 2009
June 2016   (final data collection date for primary outcome measure)
  • Event-free survival [ 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 ] [ Designated as safety issue: No ]
    Estimated by the method of Kaplan and Meier.
  • Incidence of adverse events graded according to CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    All Grade 3 or 4 or greater non-hematological toxicities as well as any toxicity that requires submission of an AdEERs report will be reported while the patient is on protocol therapy. The frequency of each toxicity type will be quantified as the percent of reporting periods on which the toxicity of the relevant grade is reported.
  • Disease status at the end of 2 courses of therapy [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
  • Disease status at the end of 2 courses of therapy [ Designated as safety issue: No ]
  • Survival rate [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00980460 on ClinicalTrials.gov Archive Site
Feasibility of referral for liver transplantation [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
A patient for whom referral is considered appropriate who receives a consultation after enrollment will be considered a success with respect to feasibility.
Feasibility of referral for liver transplantation [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Liver Cancer
Treatment of Children With All Stages of Hepatoblastoma

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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Childhood Hepatoblastoma
  • Stage I Childhood Liver Cancer
  • Stage II Childhood Liver Cancer
  • Stage III Childhood Liver Cancer
  • Stage IV Childhood Liver Cancer
  • Procedure: therapeutic conventional surgery
    Undergo surgery
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: fluorouracil
    Given IV
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: irinotecan hydrochloride
    Given IV
    Other Names:
    • Campto
    • Camptosar
    • CPT-11
    • irinotecan
    • U-101440E
  • Procedure: liver transplantation
    Undergo liver transplant
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Very low-risk group
    Patients undergo therapeutic conventional surgery and then receive no further treatment.
    Interventions:
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
  • Experimental: 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.
    Interventions:
    • Procedure: therapeutic conventional surgery
    • Drug: cisplatin
    • Drug: fluorouracil
    • Drug: vincristine sulfate
    • Other: laboratory biomarker analysis
  • Experimental: 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.
    Interventions:
    • Procedure: therapeutic conventional surgery
    • Drug: cisplatin
    • Drug: fluorouracil
    • Drug: vincristine sulfate
    • Drug: doxorubicin hydrochloride
    • Procedure: liver transplantation
    • Other: laboratory biomarker analysis
  • Experimental: 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. Responding patients then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block and non-responding patients 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.
    Interventions:
    • Procedure: therapeutic conventional surgery
    • Drug: cisplatin
    • Drug: fluorouracil
    • Drug: vincristine sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: irinotecan hydrochloride
    • Procedure: liver transplantation
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
216
Not Provided
June 2016   (final data collection date for primary outcome measure)

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
Both
up to 21 Years
No
Not Provided
United States,   Australia,   Brazil,   Canada,   Puerto Rico
 
NCT00980460
AHEP0731, NCI-2011-01975, CDR0000654889, COG-AHEP0731, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Howard Katzenstein Children's Oncology Group
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP