This early phase I trial is to assess the side effects and efficacy of a type of non-cross-reactive chemotherapy called N9 in patients with high-risk neuroblastoma. Neuroblastoma is the most common extracranial solid tumor of childhood, and while intensive induction chemotherapy and aggressive surgery have improved rates of major responses, outcomes for high-risk neuroblastoma remain unsatisfactory. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. N9 chemotherapy includes three different chemotherapy combinations and is based on recent encouraging experience with other novel regimens. N9 chemotherapy has the potential to address the drawbacks of other kinds of chemotherapy. This trial assesses whether N9 is a safe and effective treatment for children with neuroblastoma.
Additional locations may be listed on ClinicalTrials.gov for NCT04947501.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To evaluate toxicity and safety of N9, including non-hematologic effects (major organs) and hematologic effects (timing of cycles).
SECONDARY OBJECTIVES:
I. To score response of high risk neuroblastoma (HR-NB) to N9, including overall response, response of metastatic disease in bone marrow (BM), and response of primary tumor.
II. To determine the rate of gross total resection of the primary tumor after cycles 3 or 4.
III. To evaluate successful collection of an adequate number of peripheral blood stem cells (PBSCs) post-cycle 3.
EXPLORATORY OBJECTIVES:
I. To assess risk of relapse in the central nervous system (CNS).
II. To assess leukemogenicity (secondary myelodysplastic syndrome or secondary leukemia).
OUTLINE:
Patients receive cyclophosphamide intravenously (IV) over 6 hours on days 1, 2, 42, 43, 77, and 78, topotecan IV over 30 minutes on days 1-4 and 77-80, and vincristine IV on days 1, 42-44, and 77, ifosfamide IV over 6 hours on days 21-25, carboplatin IV over 1 hour on days 21 and 22, etoposide IV over 24 hours on days 21-25, and doxorubicin IV over 24 hours on days 42-44. Treatment repeat every 21-28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and bone marrow biopsy throughout the study and as clinically indicated. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI), iobenguane (MIBG) and/or positron emission tomography (PET) throughout the study and as clinically indicated.
After completion of study treatment, patients are followed up with for 45 days or until they start a new treatment, whichever is later.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorBrian Harris Kushner
