Abstract
N9: Pilot study of novel shortened induction for high-risk neuroblastoma.
Author
person
Brian H. Kushner
Memorial Sloan Kettering Cancer Center, New York, NY
info_outline
Brian H. Kushner, Audrey Mauguen, Ellen M. Basu, Fiorella Iglesias Cardenas, Justin T Gerstle, Kim Kramer, Shakeel Modak
Full text
Authors
person
Brian H. Kushner
Memorial Sloan Kettering Cancer Center, New York, NY
info_outline
Brian H. Kushner, Audrey Mauguen, Ellen M. Basu, Fiorella Iglesias Cardenas, Justin T Gerstle, Kim Kramer, Shakeel Modak
Organizations
Memorial Sloan Kettering Cancer Center, New York, NY
Abstract Disclosures
Research Funding
Memorial Sloan Kettering Cancer Center
Background:
N9 induction for high-risk neuroblastoma was designed to limit non-hematological toxicity (especially ototoxicity) and to prevent relapse in the central nervous system (CNS). N9 builds on 2 novel regimens: high-dose cyclophosphamide-topotecan-vincristine (CTV) and ifosfamide-carboplatin-etoposide (ICE), each with good penetration across the blood-brain barrier.
Methods:
N9 is a pilot study (Clinicaltrials.gov.NCT04947501) to assess feasibility and safety. Secondary/exploratory objectives include response, collection of peripheral blood stem cells (PBSCs; ≥5x10
6
/kg CD34(+) cells sufficient for ≥2 rescues), tumor resection, and assessment of central nervous system relapse. Early stopping rules centered on excessive delay in timing of chemotherapy. Eligibility criteria included age >1-to-<13 years; 1 prior chemotherapy cycle was allowed. CTCAE Version 5.0 and International Neuroblastoma Response Criteria are used.N9 comprises 4 cycles of chemotherapy. Cycles start after absolute neutrophil count is >500/μL, platelets >100,000/μL, and non-hematologic toxicities grade ≤2. Intervals of 21-28 days between start of cycles are foreseen. PBSC collection and surgery follow >3 cycles. Cycles #1 and #4 (CTV): cyclophosphamide 70mg/kg/day, days 1-2, topotecan 2mg/m
2
/day, days 1-4, and vincristine 0.067mg/kg, day 1. Cycle #2 (ICE): ifosfamide 1500mg/m
2
/day, days 1-5, carboplatin 400mg/m
2
/day, days 1-2, and etoposide 100mg/m
2
/day, days 1-5. Cycle #3: cyclophosphamide (as in CTV) and 72-hr infusions of doxorubicin 75mg/m
2
and vincristine 0.067mg/kg.
Results:
The target number of 15 patients were enrolled: 10/2021-9/2023; age 1.5–9.8 (median 3.3) years; 14 stage M, 1 stage L2; and 10 post-1 cycle of other chemotherapy. They completed N9 without undue toxicity: all cycles started on time, organ functions remained intact, 11/11 patients tested had no ototoxicity, and acute toxicities were typical for myelosuppression (including uncomplicated fever/neutropenia). Responses were complete (n=6), partial (n=5), and stable disease (n=4). The target number of PBSCs was collected in 12 patients (9-75, median 14 x10
6
/kg CD34(+) cells), 4x10
6
/kg in 2 patients, and pending in 1. All patients had gross total resections of the primary tumor. Post-N9, patients did not undergo transplant, but proceeded to immunotherapy (naxitamab) or chemoimmunotherapy (naxitamab+irinotecan-temozolomide). Of 9 with residual disease post-N9, 7 achieved CR (median of 5.6 months from study entry) and 1 achieved metabolic CR (16 months), though 3 subsequently relapsed (no CNS).
Conclusions:
N9 shows promise for reducing chemotherapy and long-term toxicity. Less chemotherapy without compromising survival is a realistic goal by virtue of the advances with anti-G
D2
monoclonal antibodies which, in combination with GM-CSF+low-dose chemotherapy, are highly effective against chemo-resistant disease in bone/bone marrow. Clinical trial information: NCT04947501.
Clinical status
Clinical
1 clinical trial
1 organization
12 drugs
7 targets
Drug
cyclophosphamideDrug
topotecanDrug
VincristineDrug
ifosfamideDrug
carboplatinDrug
etoposideDrug
doxorubicinDrug
naxitamabDrug
IrinotecanDrug
temozolomideTarget
tubulinTarget
Topoisomerase IITarget
GD2Target
DNATarget
topoisomerase IDrug
naxitamabDrug
temozolomideTarget
GM-CSFOrganization
Memorial Sloan Kettering Cancer CenterClinical trial
N9: Pilot Study of Novel Shortened Induction Chemotherapy for High-Risk NeuroblastomaStatus: Recruiting, Estimated PCD: 2025-06-22