Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
Ganglioneuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma
About this trial
This is an interventional treatment trial for Ganglioneuroblastoma
Eligibility Criteria
Inclusion Criteria:
Patients must be:
- < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
- < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms neuroblastoma/ganglioneuroblastoma
- Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
- Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
- "Favorable" genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above
- "Unfavorable" genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)
- Only patients with MYCN non-amplified tumors are eligible for this study
Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
- Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
- Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma
- No prior tumor resection or biopsy
Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
Group A1:
- > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR
- Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR
- < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter
- Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
- No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.]); horner syndrome is not considered neurologic compromise
- No prior tumor resection, tumor biopsy ONLY
- Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1 or APEC14B1
- Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms neuroblastoma/ganglioneuroblastoma
- No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
- 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:
- Patients with MYCN amplified tumors are not eligible
- Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
- Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study
Sites / Locations
- Children's Hospital of Alabama
- USA Health Strada Patient Care Center
- Providence Alaska Medical Center
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Banner University Medical Center - Tucson
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- City of Hope Comprehensive Cancer Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Cedars Sinai Medical Center
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Rady Children's Hospital - San Diego
- Naval Medical Center -San Diego
- UCSF Medical Center-Mission Bay
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital Colorado
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Connecticut Children's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Broward Health Medical Center
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- Miami Cancer Institute
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Sacred Heart Hospital
- Johns Hopkins All Children's Hospital
- Tampa General Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Augusta University Medical Center
- Memorial Health University Medical Center
- Kapiolani Medical Center for Women and Children
- Tripler Army Medical Center
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Loyola University Medical Center
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park Ridge
- Saint Jude Midwest Affiliate
- Southern Illinois University School of Medicine
- IU Health North Hospital
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Blank Children's Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Maine Children's Cancer Program
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Tufts Children's Hospital
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- Baystate Medical Center
- UMass Memorial Medical Center - University Campus
- C S Mott Children's Hospital
- Children's Hospital of Michigan
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical Center
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Spectrum Health at Butterworth Campus
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Beaumont Children's Hospital-Royal Oak
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Columbia Regional
- Children's Mercy Hospitals and Clinics
- Cardinal Glennon Children's Medical Center
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- University Medical Center of Southern Nevada
- Sunrise Hospital and Medical Center
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Renown Regional Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Hackensack University Medical Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- University of New Mexico Cancer Center
- Albany Medical Center
- Montefiore Medical Center - Moses Campus
- Maimonides Medical Center
- Roswell Park Cancer Institute
- NYU Winthrop Hospital
- The Steven and Alexandra Cohen Children's Medical Center of New York
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- University of Rochester
- State University of New York Upstate Medical University
- New York Medical College
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Duke University Medical Center
- East Carolina University
- Wake Forest University Health Sciences
- Sanford Broadway Medical Center
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Penn State Children's Hospital
- Children's Hospital of Philadelphia
- Saint Christopher's Hospital for Children
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Medical University of South Carolina
- Prisma Health Richland Hospital
- BI-LO Charities Children's Cancer Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- Saint Jude Children's Research Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- Dell Children's Medical Center of Central Texas
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- El Paso Children's Hospital
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Covenant Children's Hospital
- UMC Cancer Center / UMC Health System
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Scott and White Memorial Hospital
- Primary Children's Hospital
- University of Vermont and State Agricultural College
- University of Virginia Cancer Center
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Virginia Commonwealth University/Massey Cancer Center
- Carilion Children's
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Mary Bridge Children's Hospital and Health Center
- Madigan Army Medical Center
- West Virginia University Charleston Division
- Edwards Comprehensive Cancer Center
- West Virginia University Healthcare
- University of Wisconsin Carbone Cancer Center
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- John Hunter Children's Hospital
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Queensland Children's Hospital
- Women's and Children's Hospital-Adelaide
- Princess Margaret Hospital for Children
- Perth Children's Hospital
- Alberta Children's Hospital
- University of Alberta Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- Janeway Child Health Centre
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
- Jim Pattison Children's Hospital
- Saskatoon Cancer Centre
- Centre Hospitalier Universitaire de Quebec
- Starship Children's Hospital
- Christchurch Hospital
- San Jorge Children's Hospital
- University Pediatric Hospital
- King Faisal Specialist Hospital and Research Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Group A (clinical observation)
Group B (clinical observation, first-line chemotherapy)
Group C (clinical observation, first-line chemotherapy)
Patients undergo clinical observation for 96 weeks in the absence of disease progression. Patients also undergo CT, MRI, and/or ultrasound throughout the trial.
Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin IV over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a PR or better is achieved, patients undergo clinical observation for 3 years. Patients also undergo CT, MRI, and/or ultrasound throughout the trial and undergo bone marrow aspiration, bone marrow biopsy, and tumor biopsy at screening and time of progression.
Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years. Patients also undergo CT, MRI, and/or ultrasound throughout the trial and undergo bone marrow aspiration, bone marrow biopsy, and tumor biopsy at screening and time of progression.