Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients with Non-high Risk Neuroblastoma
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
Alabama
Birmingham
Mobile
Alaska
Anchorage
Arizona
Mesa
Phoenix
Tucson
Arkansas
Little Rock
California
Downey
Duarte
Loma Linda
Long Beach
Los Angeles
Madera
Oakland
Orange
Palo Alto
Sacramento
San Diego
San Francisco
Torrance
Colorado
Aurora
Denver
Connecticut
Hartford
New Haven
Delaware
Wilmington
District of Columbia
Washington
Florida
Fort Lauderdale
Fort Myers
Gainesville
Hollywood
Jacksonville
Miami
Orlando
Pensacola
Saint Petersburg
Tampa
West Palm Beach
Georgia
Atlanta
Augusta
Savannah
Hawaii
Honolulu
Idaho
Boise
Illinois
Chicago
Maywood
Oak Lawn
Park Ridge
Peoria
Springfield
Indiana
Carmel
Indianapolis
Iowa
Des Moines
Iowa City
Kentucky
Lexington
Louisville
Louisiana
New Orleans
Maine
Bangor
Scarborough
Maryland
Baltimore
Bethesda
Massachusetts
Boston
Springfield
Worcester
Michigan
Ann Arbor
Detroit
East Lansing
Flint
Grand Rapids
Kalamazoo
Royal Oak
Minnesota
Minneapolis
Rochester
Mississippi
Jackson
Missouri
Columbia
Kansas City
Saint Louis
Nebraska
Omaha
Nevada
Las Vegas
Reno
New Hampshire
Lebanon
New Jersey
Hackensack
Morristown
New Brunswick
Newark
Paterson
New Mexico
Albuquerque
New York
Albany
Bronx
Brooklyn
Buffalo
Mineola
New Hyde Park
New York
Rochester
Syracuse
Valhalla
North Carolina
Asheville
Chapel Hill
Charlotte
Durham
Greenville
Winston-Salem
North Dakota
Fargo
Ohio
Akron
Cincinnati
Cleveland
Columbus
Dayton
Toledo
Oklahoma
Oklahoma City
Oregon
Portland
Pennsylvania
Allentown
Bethlehem
Danville
Hershey
Philadelphia
Pittsburgh
Puerto Rico
San Juan
Rhode Island
Providence
South Carolina
Charleston
Columbia
Greenville
South Dakota
Sioux Falls
Tennessee
Chattanooga
Knoxville
Memphis
Nashville
Texas
Austin
Corpus Christi
Dallas
El Paso
Fort Worth
Houston
Lubbock
San Antonio
Temple
Utah
Salt Lake City
Vermont
Burlington
Virginia
Charlottesville
Falls Church
Norfolk
Richmond
Roanoke
Washington
Seattle
Spokane
Tacoma
West Virginia
Charleston
Morgantown
Wisconsin
Madison
Marshfield
Milwaukee
Alberta
Calgary
Edmonton
British Columbia
Vancouver
Manitoba
Winnipeg
Newfoundland and Labrador
Saint John's
Nova Scotia
Halifax
Ontario
Hamilton
Kingston
London
Ottawa
Toronto
Quebec
Montreal
Quebec
Saskatchewan
Saskatoon
Australia
Hunter Regional Mail Centre
North Adelaide
Perth
Randwick
South Brisbane
Westmead
New Zealand
Christchurch
Grafton
Saudi Arabia
Riyadh
PRIMARY OBJECTIVES:
I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.
II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and genomic features) while maintaining an OS of 99%.
III. To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.
EXPLORATORY OBJECTIVES:
I. To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation.
II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease.
III. To define the genomic profile of tumors from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.
IV. To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
V. To determine the salvage rate (OS) of patients with tumor relapse or disease progression.
VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection.
VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy.
OUTLINE: Patients are assigned to 1 of 3 treatment groups.
GROUP A: Patients undergo clinical observation for 96 weeks in the absence disease progression.
GROUP B: 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 intravenously (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 partial response (PR) or better is achieved, patients undergo clinical observation for 3 years.
GROUP C: 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.
After completion of study treatment, patients are followed up annually for up to 10 years post-enrollment.
Trial Phase Phase III
Trial Type Treatment
Lead Organization
Children's Oncology Group
Principal Investigator
Holly Jane Meany
- Primary ID ANBL1232
- Secondary IDs NCI-2014-00677, s15-00462
- Clinicaltrials.gov ID NCT02176967