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Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Liver Cancer

This study is currently recruiting participants.
Verified June 2013 by Children's Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00980460
First received: September 18, 2009
Last updated: June 10, 2013
Last verified: June 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
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
Drug: cisplatin
Drug: fluorouracil
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Drug: irinotecan hydrochloride
Procedure: liver transplantation
Other: laboratory biomarker analysis
 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Children With All Stages of Hepatoblastoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 216
Study Start Date: September 2009
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Very low-risk group
Patients undergo therapeutic conventional surgery and then receive no further treatment.
 Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies
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.
 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
Other: laboratory biomarker analysis
Correlative studies
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.
 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
Procedure: liver transplantation
Undergo liver transplant
Other: laboratory biomarker analysis
Correlative studies
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.
 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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00980460

  Show 171 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Howard Katzenstein Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00980460     History of Changes
Other Study ID Numbers: AHEP0731, NCI-2011-01975, CDR0000654889, COG-AHEP0731, U10CA098543
Study First Received: September 18, 2009
Last Updated: June 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Neoplasms
Hepatoblastoma
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Irinotecan
Cisplatin
Doxorubicin
Fluorouracil
Vincristine
Camptothecin
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on June 18, 2013