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.