Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
Childhood Hepatocellular Carcinoma, Childhood Malignant Liver Neoplasm, Fibrolamellar Carcinoma
About this trial
This is an interventional treatment trial for Childhood Hepatocellular Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must be newly diagnosed with histologically-proven primary pediatric hepatic malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified, should be classified and treated per hepatoblastoma treatment arms; note that rapid central pathology review is required in some cases; please note: all patients with histology as assessed by the institutional pathologist consistent with pure small cell undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by immunohistochemistry (IHC) according to the practices at the institution
- Patients with histology consistent with pure SCU must have positive INI1/SMARCB1 staining
For all Group A patients, WDF status as determined by rapid review will be used to further stratify patients to Group A1 or A2
- For Groups B, C and D, rapid review is required if patients are either >= 8 years of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
- For all Groups E and F patients, rapid central pathology review is required
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy
Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:
- Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
- Uncorrectable coagulopathy
For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:
- The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment
- Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment
- Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
- Patients may have had surgical resection of the hepatic malignancy prior to enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 or
A serum creatinine based on age/gender as follows:
- Age: maximum serum creatinine (mg/dL)
- 1 month to < 6 months: 0.4 (male and female)
- 6 months to < 1 year: 0.5 (male and female)
- 1 to < 2 years: 06 (male and female)
- 2 to < 6 years: 0.8 (male and female)
- 6 to < 10 years: 1 (male and female)
- 10 to < 13 years: 1.2 (male and female)
- 13 to < 16 years: 1.5 (male), 1.4 (female)
- >= 16 years: 1.7 (male), 1.4 (female)
- Total bilirubin =< 5 x upper limit of normal (ULN) for age
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 10 x upper limit of normal (ULN) for age
- Shortening fraction of >= 28% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment) or
- Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment)
- Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males and =< 470 milliseconds for females (assessed within 8 weeks prior to study enrollment)
- Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy [Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible
- Patients who are currently receiving another investigational drug
- Patients who are currently receiving other anticancer agents
- Patients with uncontrolled infection
- Patients who previously received a solid organ transplant, other than those who previously received an orthotopic liver transplantation (OLT) as primary treatment of their hepatocellular carcinoma
- Patients with hypersensitivity to any drugs on their expected treatment arm
- Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
Group D:
- Patients with chronic inflammatory bowel disease and/or bowel obstruction
- Patients with concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
Group F:
- Patients with peripheral sensitive neuropathy with functional impairment
- Patients with a personal or family history of congenital long QT syndrome
These criteria apply ONLY to patients who may receive chemotherapy (all groups other than Group E1):
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
- Lactating females who plan to breastfeed their infants
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
- Note for Group F: patients of childbearing potential should use effective birth control during treatment with sorafenib and for at least 2 weeks after stopping treatment
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- Providence Alaska Medical CenterRecruiting
- Banner Children's at DesertRecruiting
- Phoenix Childrens HospitalRecruiting
- Arkansas Children's HospitalRecruiting
- Kaiser Permanente Downey Medical CenterRecruiting
- Loma Linda University Medical CenterRecruiting
- Miller Children's and Women's Hospital Long BeachRecruiting
- Children's Hospital Los AngelesRecruiting
- Mattel Children's Hospital UCLARecruiting
- Valley Children's HospitalRecruiting
- UCSF Benioff Children's Hospital OaklandRecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- Lucile Packard Children's Hospital Stanford UniversityRecruiting
- Sutter Medical Center SacramentoRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Rady Children's Hospital - San DiegoRecruiting
- Naval Medical Center -San DiegoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital ColoradoRecruiting
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterRecruiting
- Connecticut Children's Medical CenterRecruiting
- Yale UniversityRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- MedStar Georgetown University HospitalRecruiting
- Children's National Medical CenterRecruiting
- Golisano Children's Hospital of Southwest FloridaRecruiting
- University of Florida Health Science Center - GainesvilleRecruiting
- Memorial Regional Hospital/Joe DiMaggio Children's HospitalRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
- Nicklaus Children's HospitalRecruiting
- AdventHealth OrlandoRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Sacred Heart HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Tampa General HospitalRecruiting
- Saint Joseph's Hospital/Children's Hospital-TampaRecruiting
- Saint Mary's HospitalRecruiting
- Children's Healthcare of Atlanta - EglestonRecruiting
- Augusta University Medical CenterRecruiting
- Memorial Health University Medical CenterRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Lurie Children's Hospital-ChicagoRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Loyola University Medical CenterRecruiting
- Advocate Children's Hospital-Oak LawnRecruiting
- Advocate Children's Hospital-Park RidgeRecruiting
- Saint Jude Midwest AffiliateRecruiting
- Southern Illinois University School of MedicineRecruiting
- Riley Hospital for ChildrenRecruiting
- Ascension Saint Vincent Indianapolis HospitalRecruiting
- Blank Children's HospitalRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Eastern Maine Medical CenterRecruiting
- Maine Children's Cancer ProgramRecruiting
- University of Maryland/Greenebaum Cancer CenterRecruiting
- Sinai Hospital of BaltimoreRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Walter Reed National Military Medical CenterRecruiting
- Tufts Children's Hospital
- Massachusetts General Hospital Cancer CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- Baystate Medical CenterRecruiting
- C S Mott Children's HospitalRecruiting
- Children's Hospital of MichiganRecruiting
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Spectrum Health at Butterworth Campus
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer Center
- Beaumont Children's Hospital-Royal OakRecruiting
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- University of Mississippi Medical CenterRecruiting
- Columbia RegionalRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Cardinal Glennon Children's Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- Mercy Hospital Saint LouisRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- University Medical Center of Southern NevadaRecruiting
- Sunrise Hospital and Medical CenterRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Summerlin Hospital Medical CenterRecruiting
- Renown Regional Medical CenterRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University HospitalRecruiting
- Newark Beth Israel Medical CenterRecruiting
- Saint Joseph's Regional Medical CenterRecruiting
- University of New Mexico Cancer CenterRecruiting
- Albany Medical CenterRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Roswell Park Cancer InstituteRecruiting
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- Laura and Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
- Mount Sinai HospitalRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- NYP/Weill Cornell Medical CenterRecruiting
- Stony Brook University Medical CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- New York Medical CollegeRecruiting
- Mission HospitalRecruiting
- UNC Lineberger Comprehensive Cancer CenterRecruiting
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- Novant Health Presbyterian Medical CenterRecruiting
- Duke University Medical CenterRecruiting
- Wake Forest University Health SciencesRecruiting
- Children's Hospital Medical Center of AkronRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Emanuel Children's HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Geisinger Medical CenterRecruiting
- Penn State Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Saint Christopher's Hospital for ChildrenRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Medical University of South CarolinaRecruiting
- Prisma Health Richland HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- East Tennessee Childrens HospitalRecruiting
- Saint Jude Children's Research HospitalRecruiting
- The Children's Hospital at TriStar CentennialRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Dell Children's Medical Center of Central TexasRecruiting
- Driscoll Children's HospitalRecruiting
- Medical City Dallas HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- El Paso Children's HospitalRecruiting
- Cook Children's Medical CenterRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- M D Anderson Cancer CenterRecruiting
- Covenant Children's HospitalRecruiting
- UMC Cancer Center / UMC Health SystemRecruiting
- Children's Hospital of San AntonioRecruiting
- Methodist Children's Hospital of South TexasRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Scott and White Memorial HospitalRecruiting
- Primary Children's HospitalRecruiting
- University of Vermont and State Agricultural CollegeRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Fairfax HospitalRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Naval Medical Center - PortsmouthRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- Madigan Army Medical CenterRecruiting
- West Virginia University Charleston DivisionRecruiting
- West Virginia University HealthcareRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Children's Hospital of WisconsinRecruiting
- John Hunter Children's HospitalRecruiting
- Sydney Children's HospitalRecruiting
- The Children's Hospital at Westmead
- Queensland Children's HospitalRecruiting
- Women's and Children's Hospital-Adelaide
- Royal Children's HospitalRecruiting
- Perth Children's HospitalRecruiting
- Alberta Children's HospitalRecruiting
- University of Alberta HospitalRecruiting
- CancerCare ManitobaRecruiting
- IWK Health CentreRecruiting
- McMaster Children's Hospital at Hamilton Health SciencesRecruiting
- Kingston Health Sciences CentreRecruiting
- Children's HospitalRecruiting
- Hospital for Sick ChildrenRecruiting
- The Montreal Children's Hospital of the MUHCRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- Jim Pattison Children's HospitalRecruiting
- Saskatoon Cancer Centre
- Centre Hospitalier Universitaire de QuebecRecruiting
- Starship Children's HospitalRecruiting
- Christchurch HospitalRecruiting
- San Jorge Children's Hospital
- University Pediatric HospitalRecruiting
- King Faisal Specialist Hospital and Research Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Experimental
Experimental
Group A1 (WDF)
GROUP A2 (NON-WDF)
GROUP B1 ARM 4-CDDP
GROUP B1 ARM 6-CDDP
GROUP B2 ARM I
GROUP B2 ARM II
GROUP C ARM C5VD
GROUP C ARM CDDP
GROUP D1
GROUP D2 ARM CE
GROUP D2 ARM VI
GROUP E1
GROUP E2 (PLADO)
GROUP F ARM 1 (PLADO)
GROUP F ARM 2 (P/GEMOX)
Patients undergo observation.
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.
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.
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.
Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 total cycles (4 pre-surgery, 2 post-surgery). After cycle 4, patients undergo surgery, then continue with 2 additional cycles of cisplatin.
Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 total cycles.
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.
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.
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.
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.
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.
Patients undergo observation only.
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.
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.
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.