Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients With Non-High-Risk Neuroblastoma
Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients With Non-High-Risk Neuroblastoma
This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.
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. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or ultrasound throughout the trial.
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. 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.
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. 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.
After completion of study treatment, patients are followed up annually for up to 10 years post-enrollment.
Inclusion Criteria:
Patients must be:
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
Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
Group A1:
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:
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:
Sacramento, California 95817, United States
Torrance, California 90502, United States
Denver, Colorado 80218, United States
Miami, Florida 33136, United States
Grand Rapids, Michigan 49503, United States
Grand Rapids, Michigan 49503, United States
Minneapolis, Minnesota 55404, United States
Lebanon, New Hampshire 03756, United States
New Brunswick, New Jersey 08903, United States
New Hyde Park, New York 11040, United States
New York, New York 10032, United States
Houston, Texas 77030, United States
Spokane, Washington 99204, United States
Madison, Wisconsin 53792, United States
Hunter Regional Mail Centre, New South Wales 2310, Australia