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

Status: Active

Description

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.

Eligibility Criteria

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

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
  • This criteria apply ONLY to patients who will receive chemotherapy (all groups other than Group E1): * Female patients who are pregnant; 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

Locations & Contacts

Alabama

Birmingham
Children's Hospital of Alabama
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Alaska

Anchorage
Providence Alaska Medical Center
Status: Active
Contact: Site Public Contact
Phone: 907-212-6871
Email: AKPAMC.OncologyResearchSupport@providence.org

Arizona

Mesa
Cardon Children's Medical Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Phoenix
Phoenix Childrens Hospital
Status: Active
Contact: Site Public Contact
Phone: 602-546-0920

Arkansas

Little Rock
Arkansas Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

California

Downey
Kaiser Permanente Downey Medical Center
Status: Active
Contact: Site Public Contact
Phone: 510-891-3400
Loma Linda
Loma Linda University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 909-558-3375
Los Angeles
Children's Hospital Los Angeles
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Mattel Children's Hospital UCLA
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Madera
Valley Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Oakland
Children's Hospital and Research Center at Oakland
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Kaiser Permanente-Oakland
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Orange
Children's Hospital of Orange County
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Sacramento
University of California Davis Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 916-734-3089
San Francisco
UCSF Medical Center-Mission Bay
Status: Active
Contact: Site Public Contact
Phone: 877-827-3222

Colorado

Aurora
Children's Hospital Colorado
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Connecticut

Hartford
Connecticut Children's Medical Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
New Haven
Yale University
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 302-651-6884
Email: dperry@nemours.org

District of Columbia

Washington
Children's National Medical Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
MedStar Georgetown University Hospital
Status: Active
Contact: Site Public Contact
Phone: 202-444-2223

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Gainesville
University of Florida Health Science Center - Gainesville
Status: Active
Contact: Site Public Contact
Phone: 352-273-8010
Email: cancer-center@ufl.edu
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Miami
Nicklaus Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
Arnold Palmer Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 321-843-2584
Email: melissa.leffin@orlandohealth.com
Nemours Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
West Palm Beach
Saint Mary's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Savannah
Memorial Health University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 912-350-7887
Email: clayter1@memorialhealth.com

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: Active
Contact: Site Public Contact
Phone: 808-983-6090

Idaho

Boise
Saint Luke's Mountain States Tumor Institute
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
Park Ridge
Advocate Children's Hospital-Park Ridge
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Peoria
Saint Jude Midwest Affiliate
Status: Active
Contact: Site Public Contact
Phone: 888-226-4343

Indiana

Indianapolis
Riley Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 800-248-1199

Iowa

Des Moines
Blank Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Louisiana

New Orleans
Children's Hospital New Orleans
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Ochsner Medical Center Jefferson
Status: Active
Contact: Site Public Contact
Phone: 504-703-8712
Email: Gregory.Johnstone@ochsner.org

Maine

Bangor
Eastern Maine Medical Center
Status: Active
Contact: Site Public Contact
Phone: 207-973-4274
Scarborough
Maine Children's Cancer Program
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu
Sinai Hospital of Baltimore
Status: Active
Contact: Site Public Contact
Phone: 410-601-6120
Email: pridgely@lifebridgehealth.org
Bethesda
Walter Reed National Military Medical Center
Status: Active
Contact: Site Public Contact
Phone: 301-319-2100

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 877-442-3324
Floating Hospital for Children at Tufts Medical Center
Status: Active
Contact: Site Public Contact
Phone: 617-636-5535

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Spectrum Health at Butterworth Campus
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Kalamazoo
Bronson Methodist Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
West Michigan Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Royal Oak
Beaumont Children's Hospital-Royal Oak
Status: Active
Contact: Site Public Contact
Phone: 248-551-0360

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Rochester
Mayo Clinic
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015

Mississippi

Jackson
University of Mississippi Medical Center
Status: Active
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Columbia
Columbia Regional
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Kansas City
Children's Mercy Hospitals and Clinics
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Saint Louis
Mercy Hospital Saint Louis
Status: Active
Contact: Site Public Contact
Phone: 314-251-7066
Washington University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
University of Nebraska Medical Center
Status: Active
Contact: Site Public Contact
Phone: 402-559-6941
Email: unmcrsa@unmc.edu

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
Summerlin Hospital Medical Center
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
University Medical Center of Southern Nevada
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-639-6918
Email: cancer.research.nurse@dartmouth.edu

New Jersey

Hackensack
Hackensack University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 201-996-2879
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: Active
Contact: Site Public Contact
Phone: 732-235-8675

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
Buffalo
Roswell Park Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-767-9355
Email: askroswell@roswellpark.org
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 212-639-7592
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 212-305-6361
Email: nr2616@cumc.columbia.edu
Stony Brook
Stony Brook University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-862-2215
Syracuse
State University of New York Upstate Medical University
Status: Active
Contact: Site Public Contact
Phone: 315-464-5476

North Carolina

Asheville
Mission Hospital Inc-Memorial Campus
Status: Active
Contact: Site Public Contact
Phone: 828-213-4150
Email: leslie.verner@msj.org
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu
Durham
Duke University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 888-275-3853
Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Site Public Contact
Phone: 336-713-6771

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Cleveland
Cleveland Clinic Foundation
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Rainbow Babies and Childrens Hospital
Status: Active
Contact: Site Public Contact
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Dayton
Dayton Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Toledo
The Toledo Hospital / Toledo Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Oregon Health and Science University
Status: In review
Contact: Site Public Contact
Phone: 503-494-1080
Email: trials@ohsu.edu

Pennsylvania

Hershey
Penn State Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Philadelphia
Children's Hospital of Philadelphia
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Saint Christopher's Hospital for Children
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

South Carolina

Columbia
Prisma Health Richland Hospital
Status: Active
Contact: Site Public Contact
Phone: 803-434-3533
Greenville
BI-LO Charities Children's Cancer Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: Active
Contact: Site Public Contact
Phone: 605-312-3320
Email: OncologyClinicalTrialsSF@SanfordHealth.org

Tennessee

Knoxville
East Tennessee Childrens Hospital
Status: Active
Contact: Site Public Contact
Phone: 865-541-8266
Memphis
St. Jude Children's Research Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Nashville
The Children's Hospital at TriStar Centennial
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Dallas
Medical City Dallas Hospital
Status: Active
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Site Public Contact
Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu
Fort Worth
Cook Children's Medical Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 713-798-1354
Email: burton@bcm.edu
M D Anderson Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-632-6789
Email: askmdanderson@mdanderson.org
San Antonio
Children's Hospital of San Antonio
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Methodist Children's Hospital of South Texas
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
University of Texas Health Science Center at San Antonio
Status: Active
Contact: Site Public Contact
Phone: 210-450-3800
Email: phoresearchoffice@uthscsa.edu

Utah

Salt Lake City
Primary Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Vermont

Burlington
University of Vermont and State Agricultural College
Status: Active
Contact: Site Public Contact
Phone: 802-656-8990
Email: rpo@uvm.edu

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 434-243-6303
Email: PAS9E@virginia.edu
Falls Church
Inova Fairfax Hospital
Status: Active
Contact: Site Public Contact
Phone: 703-208-6650
Email: Stephanie.VanBebber@inova.org
Norfolk
Children's Hospital of The King's Daughters
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: Active
Contact: Site Public Contact
Email: mwellons@vcu.edu

Washington

Seattle
Seattle Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Tacoma
Madigan Army Medical Center
Status: Active
Contact: Site Public Contact
Phone: 253-968-0129
Email: mamcdci@amedd.army.mil
Mary Bridge Children's Hospital and Health Center
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

West Virginia

Morgantown
West Virginia University Healthcare
Status: Active
Contact: Site Public Contact
Phone: 304-293-7374
Email: cancertrialsinfo@hsc.wvu.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922
Marshfield
Marshfield Medical Center-Marshfield
Status: Active
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Milwaukee
Children's Hospital of Wisconsin
Status: Active
Contact: Site Public Contact
Phone: 414-955-4727
Email: MACCCTO@mcw.edu

Alberta

Calgary
Alberta Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Nova Scotia

Halifax
IWK Health Centre
Status: Active
Contact: Site Public Contact
Phone: 902-470-6767

Saskatchewan

Saskatoon
Saskatoon Cancer Centre
Status: Active
Contact: Site Public Contact
Phone: 306-655-2914

Australia

Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
North Adelaide
Women's and Children's Hospital-Adelaide
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Parkville
Royal Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Perth
Perth Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Randwick
Sydney Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Westmead
The Children's Hospital at Westmead
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To reduce therapy associated toxicity for patients with non-metastatic hepatoblastoma (HB) and hepatocellular carcinoma (HCC) without adversely affecting long term outcomes.

II. To determine the event-free survival (EFS) in patients with HB whose tumor is completely resected at diagnosis and either receive no adjuvant chemotherapy (completely resected well differentiated fetal histology HB) or 2 cycles of standard dose cisplatin monotherapy (completely resected non-well differentiated fetal histology HB – 100 mg/m^2/cycle given 3 weeks apart). (Group A)

III. To demonstrate that 4 to 6 cycles of interval compressed lower dose cisplatin monotherapy (80 mg/m^2/cycle; 320 480 mg/m^2 total) is adequate for low risk HB. (Group B)

IV. In patients who are resected after 2 cycles of cisplatin monotherapy, to compare EFS following a randomized comparison of 2 versus 4 post-operative cycles of cisplatin monotherapy. (Group B)

V. In patients whose tumors are deemed unresectable after 2 cycles of cisplatin monotherapy, to determine the proportion of tumors rendered completely resectable by an additional 2 or 4 cycles of chemotherapy. (Group B)

VI. To compare in a randomized fashion, EFS in patients with intermediate risk HB treated with 6 cycles of cisplatin/5-fluorouracil/vincristine/doxorubicin (C5VD) chemotherapy versus 6 cycles of interval compressed cisplatin monotherapy (100 mg/m^2/dose). (Group C)

VII. To determine the EFS in patients with HCC whose tumor is completely resected at diagnosis who receive no adjuvant chemotherapy (completely resected HCC arising in the context of underlying liver disease) or 4 cycles of cisplatin/doxorubicin (PLADO) (completely resected de novo HCC). (Group E)

VIII. To improve the EFS of patients with high risk HB by treating them with interval compressed cisplatin and doxorubicin based induction regimen followed by response-adapted consolidation therapy. (Group D)

IX. In patients whose metastatic disease resolves with the administration of Societe Internationale d’Oncologie Pediatrique (SIOPEL) 4 Induction therapy, to determine if the promising pilot results observed in SIOPEL 4 can be validated in a large international study. (Group D1)

X. In patients whose metastatic disease does not resolve with the administration of SIOPEL 4 Induction therapy, to determine in a randomized comparison which post induction treatment (irinotecan and vincristine sulfate [vincristine] alternating with carboplatin and doxorubicin or carboplatin and etoposide alternating with carboplatin and doxorubicin) results in superior outcomes. (Group D Arm CE & Arm VI)

XI. In patients with unresectable/metastatic HCC at diagnosis, to determine whether the addition of gemcitabine and oxaliplatin (GEMOX + sorafenib) to a cisplatin, doxorubicin and sorafenib backbone improves chemotherapy response, resectability and survival. (Group F)

SECONDARY OBJECTIVES:

I. Molecular characterization of HB tumors to validate newly identified molecular and immunohistochemical biomarkers correlating with known clinical prognostic factors and outcome. (Group A-D)

II. To determine whether the molecular profile of pediatric HCC overlaps with HB or adult-type HCC while correlating biologic features with treatment response and survival. (Group E and F)

III. To define the prognostic relevance in HB of a ‘small cell undifferentiated’ tumor component and percentage of tumor necrosis in post chemotherapy specimens.

IV. To determine the concordance of Pretreatment Extent of Disease (PRETEXT) and Post-treatment Extent of disease (POSTTEXT) based surgical guidelines and the surgical intervention performed.

V. To determine which system (Children's Oncology Group [COG] PRETEXT, SIOPEL PRETEXT, or a new hybrid definition of PRETEXT) of the annotation factors for V, P, E, F and R provides the best prognostic information for determining response to chemotherapy, guiding risk based therapy, predicting surgical resectability, and EFS.

VI. To determine the concordance between institutional and expert panel review assessment of PRETEXT and POSTTEXT stage in an international cooperative group setting.

VII. To assess clinical characteristics, basic chemotherapy and surgical treatment details, biological characteristics at baseline and recurrence (when available) and outcome of patients with refractory or relapsed hepatoblastoma after initial treatment.

VIII. To identify novel biomarkers of renal toxicity (urine NGAL, cystatin C and Kim1) from cisplatin therapy when given according to the regimens used on this study, and to correlate such biomarkers with pharmacogenomics, other associated toxicities, and outcomes.

TERTIARY OBJECTIVES:

I. To determine if the Childhood Hepatic tumor International Consortium (CHIC) hepatoblastoma risk stratification analysis of very low risk (Group A), low risk (Group B), intermediate risk (Group C) and high risk (Group D) groups stratifies patients allowing appropriate utilization of varying intensity chemotherapy regimens and surgical resection strategies.

II. To define the prognostic relevance of a positive microscopic margin in Group A-D resected HB specimens.

III. To define the frequency of histologically detectable multifocal lesions in liver explants and resected specimens in which multifocal disease was detected at diagnosis and disappeared on cross sectional imaging following treatment with chemotherapy.

IV. To determine the prognostic impact on EFS and overall survival (OS) of biopsy technique in liver tumors unresectable at diagnosis.

V. To determine the frequency of intraoperative complications from surgery for local control (conventional resection or liver transplantation) and its impact on EFS.

VI. To determine the 3-year EFS and OS of HB patients who undergo liver transplantation versus (vs) extreme resection in Group C and D patients.

VII. To determine the 3-year EFS and OS of Group D patients who undergo pulmonary metastatectomy.

VIII. To determine the 3-year EFS and OS of patients who undergo liver transplantation for HCC.

IX. To determine the frequency of relapse in non-metastatic HCC in children treated by liver transplantation versus conventional resection.

X. To assess the pharmacogenomics (PG) related to cisplatin therapy in pediatric and adolescent liver tumor patients and correlate PG with Boston Grading Scale for ototoxicity.

OUTLINE:

GROUP A (VERY LOW RISK HB): Patients are assigned to 1 of 2 groups.

GROUP A1 (WELL-DIFFERENTIATED FETAL [WDF]): Patients undergo observation.

GROUP A2 (NON-WDF): Patients receive cisplatin (CDDP) intravenously (IV) over 6 hours on day 1 following surgery. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

GROUP B (LOW RISK HB): Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients are then assigned to 1 of 2 groups

GROUP B1 (RESECTABLE): Patients undergo surgery, then are randomized to 1 of 2 arms.

GROUP B1 ARM 4-CDDP: Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

GROUP B1 ARM 6-CDDP: Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

GROUP B2 (UNRESECTABLE): Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 2 courses. Patients with resectable tumors undergo surgery, then all patients continue with 2 additional courses of cisplatin.

GROUP C (INTERMEDIATE RISK HB): Patients are randomized to 1 of 2 arms.

GROUP C ARM CDDP: Patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after course 2.

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 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after course 2.

GROUP D (HIGH RISK HB): SIOPEL-4 IV INDUCTION: Patients receive cisplatin IV over 6 hours on days 1, 8, and 15 (for courses 1 and 2) and days 1 and 8 (for course 3) and doxorubicin IV over 1-15 minutes on days 8 and 9. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are then assigned to 1 of 2 arms.

GROUP D1: CONSOLIDATION THERAPY: 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 courses in the absence of disease progression or unacceptable toxicity.

GROUP D2: Patients with residual metastatic disease are randomized to 1of 2 arms.

GROUP D2 ARM CE: Patients receive carboplatin IV over 1 hour on days 1 and 2, doxorubicin IV over 1-15 minutes on days 1 and 2 during courses 1, 3 and 5, and etoposide IV over 2 hours on day 1 and 2 of courses 2, 4 and 6. Treatments repeat every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

GROUP D2 ARM VI: 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 courses 1, 3 and 5. Patients also receive vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan IV over 90 minutes once daily (QD) on days 1 to 5 of courses 2, 4 and 6. Treatments repeat every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

GROUP E (RESECTED HCC): Patients are assigned to 1 of 2 groups.

GROUP E1: Patients with HCC secondary to disease undergo observation only.

GROUP E2 (PLADO): Patients with de novo HCC 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 up to 4 courses in the absence of disease progression or unacceptable toxicity.

GROUP F (UNRESECTED AND/OR METASTATIC HCC): Patients are randomized to 1 of 2 arms.

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 orally (PO) twice daily (BID) on days 3-21. Treatments repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo surgery, if tumors are resectable, or receive an additional 3 courses of the treatment.

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 courses 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 courses 2 and 4. Patients may undergo surgery, if tumors are resectable, or receive an additional 4 courses of the treatment.

After completion of study treatment, patients are followed up for a minimum of 2 years.

Trial Phase & Type

Trial Phase

Phase II/III

Trial Type

Treatment

Lead Organization

Lead Organization
Childrens Oncology Group

Principal Investigator
Gregory M. Tiao

Trial IDs

Primary ID AHEP1531
Secondary IDs NCI-2017-01910
Clinicaltrials.gov ID NCT03533582