A Phase 3 interventional study of Biopsy and Bone Marrow Aspiration in Ganglioneuroblastoma, Localized Resectable Neuroblastoma and Localized Unresectable Neuroblastoma, sponsored by Children's Oncology Group. Active, not recruiting at 222 sites in 6 countries. Open to participants aged Up to 18 Months. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by Children's Oncology Group · Phase 3, Interventional, and Treatment
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.
23 studies on the registry are indexed under Ganglioneuroblastoma; 10 are open to participants now.
This study's planned enrollment of 621 is above the median of 71 across 18 interventional studies indexed under Ganglioneuroblastoma.
Browse Ganglioneuroblastoma studies →Children's Oncology Group is the lead sponsor of 436 studies on the registry; 34 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients must be:
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 B: patients \< 18 months (\< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
Exclusion Criteria:
Patients undergo clinical observation for 96 weeks in the absence of disease progression. Patients also undergo CT, MRI, and/or ultrasound throughout the trial.
Other: Clinical Observation · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Ultrasound
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.
Procedure: Biopsy · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Carboplatin · Other: Clinical Observation · Procedure: Computed Tomography · Drug: Cyclophosphamide · Drug: Doxorubicin Hydrochloride · Drug: Etoposide · Procedure: Magnetic Resonance Imaging · Procedure: Ultrasound
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.
Procedure: Biopsy · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Carboplatin · Other: Clinical Observation · Procedure: Computed Tomography · Drug: Cyclophosphamide · Drug: Doxorubicin Hydrochloride · Drug: Etoposide · Procedure: Magnetic Resonance Imaging · Procedure: Ultrasound
Undergo biopsy
Also known as: BIOPSY_TYPE, Bx
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Given IV
Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Undergo clinical observation
Also known as: observation
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719
Given IV
Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex
Given IV
Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Undergo ultrasound
Overall survival (OS) (Strata 1-4)
The Kaplan-Meier method will be used to estimate the 3-year overall survival for each stratum. OS is measured from time of enrollment to the date of death from any cause.
Time frame: From date of enrollment until death or last contact, assessed up to 3 years
Time to intervention or tumor progression
Will be assessed by a descriptive analysis for the cohort of patients with localized tumors who progress after an initial period of observation.
Time frame: Up to 3 years
Type of intervention required
Will be assessed by a descriptive analysis for the cohort of patients with localized tumors who progress after an initial period of observation.
Time frame: Up to 3 years
Site of progression
Will be assessed by a descriptive analysis for the cohort of patients with localized tumors who progress after an initial period of observation.
Time frame: Up to 3 years
Pharmacokinetic (PK) profile of carboplatin and etoposide in patients with stage Ms disease, including peak concentration, area under the curve, clearance, volume of distribution, half-life, and mean residence time
The coefficient of variation will be calculated to quantify the degree of inter-patient and intra-patient variability of etoposide and carboplatin PK. The relationship between patient characteristics will be assessed graphically in an exploratory fashion and with regression models and if appropriate, Spearman's rank correlation coefficient will be used. Correlations between PK parameters and the symptom score and hepatic and renal dysfunction will be explored. Logistic regression models adjusting for patient level covariates will be explored.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours on days 1 and 2 of either course 1 or 7
Genomic profile of tumors
Will be assessed by determining the presence or absence of each segmental aberration (segmental loss at 1p, 3p, 4p, or 11q or segmental gain at 1p, 2p, or 17q), both at initial biopsy and at the time of subsequent biopsy or surgical resection, and correlating with patient characteristics using a chi-squared test and with outcome using a log-rank test. In cases with specimens from diagnosis and at the time of subsequent biopsy/resection, the profiles will be compared focusing on changes in the copy number pattern.
Time frame: Up to time of biopsy or surgical resection
Histology of tumor specimens
Will be assessed by a descriptive analysis of the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
Time frame: Up to time of biopsy or surgical resection
Salvage rate (overall survival [OS]) of patients with tumor relapse or disease progression
Will be assessed by calculating the overall survival for the cohort of patients with tumor relapse or disease progression.
Time frame: From the date of enrollment until death or until last contact if the patient is alive, assessed up to 3 years
Procedural complication rate
Will be assessed by determining the complication rate for each type of procedure (initial biopsy and resection \[intraoperative and postoperative\]) and correlating the occurrence of surgical complications with the degree of surgical resection using a Wilcoxon rank-sum test (to account for the ordering of the surgical resection categories).
Time frame: Up to 60 days after surgery
Rate of reduction in Image Defined Risk Factors (IDRF) in L2 tumors
Will be assessed by computing the proportion of patients with L2 tumors for which each particular IDRF and any IDRF is present at diagnosis and then absent after observation or chemotherapy. In addition, McNemar's test for paired observations will be applied to determine whether there is a difference in the proportion of each IDRF and any IDRF present before and after observation or chemotherapy.
Time frame: Up to 3 years
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Children's Oncology Group