Purpose

This partially randomized phase II/III trial studies how well, in combination with surgery, cisplatin and combination chemotherapy works in treating children and young adults with hepatoblastoma or hepatocellular carcinoma. Drugs used in chemotherapy, such as cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy may kill more tumor cells than one type of chemotherapy alone.

Category

IRB Number
20180532HU
NCT Number
NCT03533582
Open to Enrollment
Yes
Sponsor
Children's Oncology Group -



Study Contact

Local Recruitment Point of Contact
Jaclyn Hung
+1 (210) 450-5358
hungj@uthscsa.edu

Principal Investigator
Anne-Marie Langevin

Regulatory Point of Contact
Virginia Diaz
(210) 562-9149
diazvr@uthscsa.edu

Regulatory Point of Contact
Jaclyn Hung
+1 (210) 450-5358
hungj@uthscsa.edu



Eligibility

Eligible Ages
Under30 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    Exclusion Criteria


      Study Design

      Phase
      Phase 2/Phase 3
      Study Type
      Interventional
      Allocation
      Randomized
      Intervention Model
      Parallel Assignment
      Primary Purpose
      Treatment
      Masking
      None (Open Label)
      Condition
    1. Childhood Hepatocellular Carcinoma
    2. Childhood Malignant Liver Neoplasm
    3. Fibrolamellar Carcinoma
    4. Hepatoblastoma
    5. Hepatocellular Malignant Neoplasm, Not Otherwise Specified
    6. Arm Groups

      ArmDescriptionIntervention
      Experimental

      GROUP A2 (NON-WDF)

      Patients receive cisplatin IV over 6 hours on day 1 following surgery. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
    7. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    8. Other: Laboratory Biomarker Analysis

      Correlative studies

    9. Experimental

      GROUP B1 ARM 6-CDDP

      Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for 6 cycles (2 pre-surgery, 4 post-surgery) in the absence of disease progression or unacceptable toxicity.
    10. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    11. Other: Laboratory Biomarker Analysis

      Correlative studies

    12. Experimental

      GROUP C ARM C5VD

      Patients receive cisplatin IV over 6 hours on day 1, 5-fluorouracil IV over 1-15 minutes, vincristine sulfate IV over 1 minute on days 1, 8, and 15 and doxorubicin IV over 1-15 minutes on days 1 and 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after cycle 2 or 4.
    13. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    14. Other: Laboratory Biomarker Analysis

      Correlative studies

    15. Drug: Vincristine Sulfate

      Given IV

      Other names:

      • Kyocristine
      • Leurocristine Sulfate
      • Leurocristine, sulfate
      • Oncovin
      • Vincasar
      • Vincosid
      • Vincrex
      • Vincristine, sulfate

    16. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    17. Drug: Fluorouracil

      Given IV

      Other names:

      • 5 Fluorouracil
      • 5 Fluorouracilum
      • 5 FU
      • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
      • 5-Fluorouracil
      • 5-Fluracil
      • 5-Fu
      • 5FU
      • AccuSite
      • Carac
      • Fluoro Uracil
      • Flu

    18. Experimental

      GROUP D1

      SIOPEL-4 INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for cycles 1 and 2) and days 1 and 8 (for cycle 3) and doxorubicin IV over 1-15 minutes on days 8 and 9 during cycles 1 and 2 and days 1 and 2 during cycle 3. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients with lung complete remission (either with chemotherapy and/or surgery) receive carboplatin IV over 1 hour on day 1 and doxorubicin IV over 1-15 minutes on days 1 and 2. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
    19. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    20. Other: Laboratory Biomarker Analysis

      Correlative studies

    21. Drug: Carboplatin

      Given IV

      Other names:

      • Blastocarb
      • Carboplat
      • Carboplatin Hexal
      • Carboplatino
      • Carboplatinum
      • Carbosin
      • Carbosol
      • Carbotec
      • CBDCA
      • Displata
      • Ercar
      • JM-8
      • Nealorin
      • Nov

    22. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    23. Experimental

      GROUP D2 ARM VI

      SIOPEL-4 IV INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for cycles 1 and 2) and days 1 and 8 (for cycle 3) and doxorubicin IV over 1-15 minutes on days 8 and 9. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients receive carboplatin IV over 1 hour on days 1 and 2 and doxorubicin IV over 1-15 minutes on days 1 and 2 during cycles 1, 3 and 5. Patients also receive vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan IV over 90 minutes QD on days 1 to 5 of cycles 2, 4 and 6. Treatments repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
    24. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    25. Other: Laboratory Biomarker Analysis

      Correlative studies

    26. Drug: Vincristine Sulfate

      Given IV

      Other names:

      • Kyocristine
      • Leurocristine Sulfate
      • Leurocristine, sulfate
      • Oncovin
      • Vincasar
      • Vincosid
      • Vincrex
      • Vincristine, sulfate

    27. Drug: Carboplatin

      Given IV

      Other names:

      • Blastocarb
      • Carboplat
      • Carboplatin Hexal
      • Carboplatino
      • Carboplatinum
      • Carbosin
      • Carbosol
      • Carbotec
      • CBDCA
      • Displata
      • Ercar
      • JM-8
      • Nealorin
      • Nov

    28. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    29. Drug: Irinotecan

      Given IV

    30. Experimental

      GROUP E2 (PLADO)

      Patients receive cisplatin IV over 6 hours on day 1 and doxorubicin IV over 1-15 minutes on days 1 and 2 following surgery. Treatments repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
    31. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    32. Other: Laboratory Biomarker Analysis

      Correlative studies

    33. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    34. Experimental

      GROUP F ARM 2 (P/GEMOX)

      Patients receive cisplatin IV over 6 hours on day 1, doxorubicin IV over 1-15 minutes on days 1 and 2 and sorafenib PO BID on days 3-14 of cycles 1 and 3. Patients also receive gemcitabine IV over 90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 and sorafenib PO on days 1-14 of cycles 2 and 4. Patients may undergo surgery, if tumors are resectable, or receive an additional 4 cycles of the treatment.
    35. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    36. Drug: Gemcitabine

      Given IV

      Other names:

      • dFdC
      • dFdCyd
      • Difluorodeoxycytidine

    37. Other: Laboratory Biomarker Analysis

      Correlative studies

    38. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    39. Drug: Oxaliplatin

      Given IV

      Other names:

      • 1-OHP
      • Ai Heng
      • Aiheng
      • Dacotin
      • Dacplat
      • Diaminocyclohexane Oxalatoplatinum
      • Eloxatin
      • Eloxatine
      • JM-83
      • Oxalatoplatin
      • Oxalatoplatinum
      • RP 54780

    40. Drug: Sorafenib

      Given PO

      Other names:

      • BA4 43 9006
      • BAY 43-9006
      • Bay-439006

    41. Active Comparator

      Group A1 (WDF)

      Patients undergo observation.
    42. Other: Laboratory Biomarker Analysis

      Correlative studies

    43. Other: Patient Observation

      Undergo watchful waiting

      Other names:

      • Active Surveillance
      • deferred therapy
      • expectant management
      • Observation
      • Watchful Waiting

    44. Experimental

      GROUP B1 ARM 4-CDDP

      Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for 4 cycles (2 pre-surgery, 2 post-surgery) in the absence of disease progression or unacceptable toxicity.
    45. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    46. Other: Laboratory Biomarker Analysis

      Correlative studies

    47. Experimental

      GROUP B2 (UNRESECTABLE)

      Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for 6 cycles (4 pre-surgery, 2 post-surgery).
    48. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    49. Other: Laboratory Biomarker Analysis

      Correlative studies

    50. Experimental

      GROUP C ARM CDDP

      Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after cycle 2 or 4.
    51. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    52. Other: Laboratory Biomarker Analysis

      Correlative studies

    53. Experimental

      GROUP D2 ARM CE

      SIOPEL-4 IV INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for cycles 1 and 2) and days 1 and 8 (for cycle 3) and doxorubicin IV over 1-15 minutes on days 8 and 9. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients receive carboplatin IV over 1 hour on days 1 and 2, doxorubicin IV over 1-15 minutes on days 1 and 2 during cycles 1, 3 and 5, and carboplatin over 1 hour and etoposide IV over 2 hours on day 1 and 2 of cycles 2, 4 and 6. Treatments repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
    54. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    55. Drug: Etoposide

      Given IV

      Other names:

      • Demethyl Epipodophyllotoxin Ethylidine Glucoside
      • EPEG
      • Lastet
      • Toposar
      • Vepesid
      • VP 16
      • VP 16-213
      • VP-16
      • VP-16-213
      • VP16

    56. Other: Laboratory Biomarker Analysis

      Correlative studies

    57. Drug: Carboplatin

      Given IV

      Other names:

      • Blastocarb
      • Carboplat
      • Carboplatin Hexal
      • Carboplatino
      • Carboplatinum
      • Carbosin
      • Carbosol
      • Carbotec
      • CBDCA
      • Displata
      • Ercar
      • JM-8
      • Nealorin
      • Nov

    58. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    59. Active Comparator

      GROUP E1

      Patients undergo observation only.
    60. Other: Laboratory Biomarker Analysis

      Correlative studies

    61. Other: Patient Observation

      Undergo watchful waiting

      Other names:

      • Active Surveillance
      • deferred therapy
      • expectant management
      • Observation
      • Watchful Waiting

    62. Experimental

      GROUP F ARM 1 (PLADO)

      Patients receive cisplatin IV over 6 hours on day 1, doxorubicin IV over 1-15 minutes on days 1 and 2 and sorafenib PO BID on days 3-21. Treatments repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo surgery, if tumors are resectable, or receive an additional 3 cycles of the treatment.
    63. Drug: Cisplatin

      Given IV

      Other names:

      • Abiplatin
      • Blastolem
      • Briplatin
      • CDDP
      • Cis-diammine-dichloroplatinum
      • Cis-diamminedichloridoplatinum
      • Cis-diamminedichloro Platinum (II)
      • Cis-diamminedichloroplatinum

    64. Other: Laboratory Biomarker Analysis

      Correlative studies

    65. Drug: Doxorubicin

      Given IV

      Other names:

      • Adriablastin
      • Hydroxydaunomycin
      • Hydroxyl Daunorubicin
      • Hydroxyldaunorubicin

    66. Drug: Sorafenib

      Given PO

      Other names:

      • BA4 43 9006
      • BAY 43-9006
      • Bay-439006