Pediatric Hepatic Malignancy International Therapeutic Trial
Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)
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Clinical Trial Information
Trial Contact: Spinelli, Jennifer; Parker, Melanie; Armatti, Julie M; Doyle, Katherine M; Dubberly, Paige D
Trial Phone: 321.841.5357 ; 321-843-1036 ; 321-843-5284 ; 3218412008 ; 321-841-7561
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IRB No: AHEP1531
Protocol Abbrev: AHEP1531
Principal Investigator: Amy A. Smith, MD
Phase: Drug: Phase II
Age Group: Pediatric
Secondary Protocol No: AHEP1531
Treatment: Drug: Carboplatin Drug: Cisplatin Drug: Doxorubicin Drug: Etoposide Drug: Fluorouracil Drug: Gemcitabine Drug: Irinotecan Other: Laboratory Biomarker Analysis Drug: Oxaliplatin Other: Patient Observation Drug: Sorafenib Drug: Vincristine Sulfate
Therapies Involved: Surgery
ClinicalTrials.gov ID: NCT03533582
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Objective
This partially randomized phase II/III trial studies how well cisplatin and combination chemotherapy works in treating children and young adults with hepatoblastoma or liver cancer after surgery. 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 after surgery may kill more tumor cells.
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Key Eligibility
Inclusion Criteria:
• 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; 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
• 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) >= 70 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]) < 10x upper limit of normal (ULN) for age
• Shortening fraction of >= 27% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E, and F]), or
• Ejection fraction of >= 50% by radionuclide angiogram (for patients on doxorubicin-containing regimens (Groups C, D, E, and F)
• 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 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
