Ireland
--:--IST
Latest
Astellas Expands Its 330 Million Euro Tralee Biopharma Facility with a Second Aseptic Filling Line to Double Drug-Product Capacity Xeolas Pharmaceuticals Opens 158,000 Sq Ft State-of-the-Art Baldoyle Facility to Scale Specialty Medicine Manufacturing Priya Life Science Partners with Fleming for the 9th Annual Corporate Compliance & Transparency in Life Sciences Summit in Zurich Ireland Has the Capital and the Lessons: Digital Project Management Is How They Become Delivery Dunbar Pharma Brings First Plant-Derived Dronabinol API to UK Market Through IPS Pharma Leveraging Priya Life Science as a Data Tracker: The Ultimate Use Case & Career Guide The €100K Reality Check: Why a Six-Figure Pharma Salary in Ireland Feels Different Than in Switzerland or Germany Ireland's €93.8 Billion Non-EU Pharma Export Engine: Trade Data, Destination Markets, and Economic Impact Astellas Expands Its 330 Million Euro Tralee Biopharma Facility with a Second Aseptic Filling Line to Double Drug-Product Capacity Xeolas Pharmaceuticals Opens 158,000 Sq Ft State-of-the-Art Baldoyle Facility to Scale Specialty Medicine Manufacturing Priya Life Science Partners with Fleming for the 9th Annual Corporate Compliance & Transparency in Life Sciences Summit in Zurich Ireland Has the Capital and the Lessons: Digital Project Management Is How They Become Delivery Dunbar Pharma Brings First Plant-Derived Dronabinol API to UK Market Through IPS Pharma Leveraging Priya Life Science as a Data Tracker: The Ultimate Use Case & Career Guide The €100K Reality Check: Why a Six-Figure Pharma Salary in Ireland Feels Different Than in Switzerland or Germany Ireland's €93.8 Billion Non-EU Pharma Export Engine: Trade Data, Destination Markets, and Economic Impact
Active, not recruiting Phase 3

Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery

NCT03533582 · tracked via the Priya Life Science Israel tracker
Phase
Phase 3
Started
2018-05-24
Last updated
2026-09-14

Condition(s) studied

Childhood Hepatocellular CarcinomaChildhood Malignant Liver NeoplasmFibrolamellar CarcinomaHepatoblastomaHepatocellular Malignant Neoplasm, Not Otherwise Specified

Investigational drug(s) / intervention(s)

Biospecimen CollectionCarboplatin →Cisplatin →Doxorubicin →Etoposide →Fluorouracil →Gemcitabine →Irinotecan →Oxaliplatin →Patient ObservationResectionSorafenib →Vincristine Sulfate →

Biospecimen Collection: Undergo blood sample collection

Carboplatin: Given IV

Cisplatin: Given IV

Doxorubicin: Given IV

Etoposide: Given IV

Fluorouracil: Given IV

Gemcitabine: Given IV

Irinotecan: Given IV

Oxaliplatin: Given IV

Patient Observation: Undergo watchful waiting

Resection: Undergo surgical resection

Sorafenib: Given PO

Vincristine Sulfate: Given IV

Study summary

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.

Eligibility

Sex
ALL
Min age
—
Max age
30 Years
Healthy volunteers
No
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

Primary outcome measure(s)

  • Event-free survival (EFS) — 3 years
    EFS is defined as the time from randomization (or registration into the trial for non-randomized patients) to the first failure event where the failure events are defined as: progression of existing disease or occurrence of disease at new sites, death from any cause prior to disease progression, or diagnosis of a second malignant neoplasm. Patients who have not had an event will be censored at their last follow-up date. EFS for group A, group B1, group C, group D1, group D2 and E will be presented.
  • Percentage of Group B2 participants with resectable tumors — At 3 years
    Group B patients who are unresectable after cycles 1 \& 2 of cisplatin treatment will be assigned to Group B2. These patients will receive cycles 3-6 of cisplatin treatment.
  • Response rate for Group F patients — After Cycle 3 for cisplatin/doxorubicin (PLADO) plus sorafenib (cycle = 21 days) or after Cycle 4 for PLADO/gemcitabine and oxaliplatin (GEMOX) plus sorafenib (cycle = 14 days)
    Response is defined as complete (CR) or partial (PR) response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be classified as non-responders.

Trial sites (205)

FacilityCityRegionStatus
Children's Hospital of Alabama Birmingham Alabama
Providence Alaska Medical Center Anchorage Alaska
Banner Children's at Desert Mesa Arizona
Phoenix Childrens Hospital Phoenix Arizona
Arkansas Children's Hospital Little Rock Arkansas
Kaiser Permanente Downey Medical Center Downey California
Loma Linda University Medical Center Loma Linda California
Miller Children's and Women's Hospital Long Beach Long Beach California
Children's Hospital Los Angeles Los Angeles California
Mattel Children's Hospital UCLA Los Angeles California
Valley Children's Hospital Madera California
UCSF Benioff Children's Hospital Oakland Oakland California
Kaiser Permanente-Oakland Oakland California
Children's Hospital of Orange County Orange California
Lucile Packard Children's Hospital Stanford University Palo Alto California
Sutter Medical Center Sacramento Sacramento California
University of California Davis Comprehensive Cancer Center Sacramento California
Rady Children's Hospital - San Diego San Diego California
Naval Medical Center -San Diego San Diego California
UCSF Medical Center-Mission Bay San Francisco California
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center Torrance California
Children's Hospital Colorado Aurora Colorado
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado
Connecticut Children's Medical Center Hartford Connecticut
Yale University New Haven Connecticut
Alfred I duPont Hospital for Children Wilmington Delaware
MedStar Georgetown University Hospital Washington D.C. District of Columbia
Children's National Medical Center Washington D.C. District of Columbia
Golisano Children's Hospital of Southwest Florida Fort Myers Florida
UF Health Cancer Institute - Gainesville Gainesville Florida
Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida
Nemours Children's Clinic-Jacksonville Jacksonville Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
Nicklaus Children's Hospital Miami Florida
AdventHealth Orlando Orlando Florida
Arnold Palmer Hospital for Children Orlando Florida
Nemours Children's Hospital Orlando Florida
Sacred Heart Hospital Pensacola Florida
Johns Hopkins All Children's Hospital St. Petersburg Florida
Tampa General Hospital Tampa Florida

+ 165 more sites — see the full list on the official registry below.

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03533582 on ClinicalTrials.gov ↗ ← All trials in Israel