A Study of N9 Chemotherapy in Children With Neuroblastoma

NCT04947501 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 21-228
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to find out whether N9 is a safe and effective treatment for children with neuroblastoma. N9 includes 3 different combinations of chemotherapy drugs that are given at different times - Cyclophosphamide, topotecan, and vincristine (CTV), Ifosfamide, carboplatin, and etoposide (ICE), Cyclophosphamide, doxorubicin, and vincristine (CDV).

Conditions

Neuroblastoma; Pediatric Cancer

Keywords

HR-NB; Neuroblastoma; pediatric cancer; 21-228; Memorial Sloan Cancer Center

Outcome Measures

Primary Outcomes (1)

• Assess safety of the N9 regimen in participants with HR-NB through toxicity assessment

  Adverse events will be graded using Common Toxicity Criteria Version 5.0 developed by the National Cancer Institute of the USA, events of all grades will be tabulated, for non-hematologic effects and hematologic effects on the patients in the safety set. The timing of cycles will also be described to assess any delay due to toxicity

  16 weeks

Study Arms (1)

Participants with newly-diagnosed HR-Neuroblastoma

EXPERIMENTAL

This pilot study of N9 as induction chemotherapy will enroll 30 patients with newly-diagnosed HR-NB. A first cohort of \>1 to 12-year old, and a second cohort of extended age \<19 years old. Both cohorts will be analyzed together.

Drug: Cyclophosphamide; Drug: Topotecan; Drug: Vincristine; Drug: Doxorubicin; Drug: Ifosfamide; Drug: Etoposide; Drug: Carboplatin; Drug: Mesna

Interventions

Cyclophosphamide DRUG

Administration of CTV - cycles 1 and 4 Days 1 \& 2: Cyclophosphamide 70 mg/kg/day (2100 mg/m2/day for patients \>10 years old), IV over 6 hrs. Mesna 70 mg/kg (2100 mg/m2/day for patients \>10 years old) , by 24-hr IV infusion, starting with the cyclophosphamide infusion. Days 1-4: Topotecan 2 mg/m2/day, IV over 30 minutes. Day 1: Vincristine 0.067 mg/kg (or 2 mg/m2, whichever is less) by IV piggyback; maximum dose is 2 mg. \*\*\*\*\*\*\* Administration of CDV - cycle 3 Days 1 \& 2: Cyclophosphamide 70 mg/kg/day ((2100 mg/m2/day for patients \>10 years old), IV over 6 hrs. Mesna 70 mg/kg ((2100 mg/m2/day for patients \>10 years old), by 24-hr IV infusion, starting with the cyclophosphamide infusion. Days 1-3: Doxorubicin 25 mg/m2/day, by 24-hr IV infusion (total dose over 72 hr is 75 mg/m2). Days 1-3: Vincristine 0.67 mg/m2/day or 0.022 mg/kg/day (whichever is less), by 24-hr IV infusion (total dose over 72 hr is 2 mg/m2 or 0.067 mg/kg); maximum dose is 0.67 mg/day, or 2mg over 72 hr.

Also known as: Cytoxan

Participants with newly-diagnosed HR-Neuroblastoma

Topotecan DRUG

Administration of CTV - cycles 1 and 4 Days 1 \& 2: Cyclophosphamide 70 mg/kg/day (2100 mg/m2/day for patients \>10 years old), IV over 6 hrs. Mesna 70 mg/kg (2100 mg/m2/day for patients \>10 years old) , by 24-hr IV infusion, starting with the cyclophosphamide infusion. Days 1-4: Topotecan 2 mg/m2/day, IV over 30 minutes. Day 1: Vincristine 0.067 mg/kg (or 2 mg/m2, whichever is less) by IV piggyback; maximum dose is 2 mg.

Also known as: Hycamtin

Participants with newly-diagnosed HR-Neuroblastoma

Vincristine DRUG

Administration of CTV - cycles 1 and 4 Days 1 \& 2: Cyclophosphamide 70 mg/kg/day (2100 mg/m2/day for patients \>10 years old), IV over 6 hrs. Mesna 70 mg/kg (2100 mg/m2/day for patients \>10 years old) , by 24-hr IV infusion, starting with the cyclophosphamide infusion. Days 1-4: Topotecan 2 mg/m2/day, IV over 30 minutes. Day 1: Vincristine 0.067 mg/kg (or 2 mg/m2, whichever is less) by IV piggyback; maximum dose is 2 mg.

Also known as: Oncovin

Participants with newly-diagnosed HR-Neuroblastoma

Doxorubicin DRUG

Administration of CDV - cycle 3 Days 1 \& 2: Cyclophosphamide 70 mg/kg/day ((2100 mg/m2/day for patients \>10 years old), IV over 6 hrs. Mesna 70 mg/kg ((2100 mg/m2/day for patients \>10 years old), by 24-hr IV infusion, starting with the cyclophosphamide infusion. Days 1-3: Doxorubicin 25 mg/m2/day, by 24-hr IV infusion (total dose over 72 hr is 75 mg/m2). Days 1-3: Vincristine 0.67 mg/m2/day or 0.022 mg/kg/day (whichever is less), by 24-hr IV infusion (total dose over 72 hr is 2 mg/m2 or 0.067 mg/kg); maximum dose is 0.67 mg/day, or 2mg over 72 hr.

Also known as: Adriamycin

Participants with newly-diagnosed HR-Neuroblastoma

Ifosfamide DRUG

Administration of ICE - cycle 2 Days 1-5: Ifosfamide 1500 mg/m2/day (50 mg/kg/day if weight is \<10 kg), IV over 6 hrs. Mesna 1500 mg/m2/day, by 24-hr IV infusion, starting with the ifosfamide infusion. Days 1-2: Carboplatin 400 mg/m2/day (13.3 mg/kg/day if weight is \<10 kg), IV over 1 hr. Days 1-5: Etoposide 100 mg/m2/day (3.3. mg/kg/day if weight is \<10 kg), IV over 2 hrs.

Also known as: Isophosphamide

Participants with newly-diagnosed HR-Neuroblastoma

Etoposide DRUG

Administration of ICE - cycle 2 Days 1-5: Ifosfamide 1500 mg/m2/day (50 mg/kg/day if weight is \<10 kg), IV over 6 hrs. Mesna 1500 mg/m2/day, by 24-hr IV infusion, starting with the ifosfamide infusion. Days 1-2: Carboplatin 400 mg/m2/day (13.3 mg/kg/day if weight is \<10 kg), IV over 1 hr. Days 1-5: Etoposide 100 mg/m2/day (3.3. mg/kg/day if weight is \<10 kg), IV over 2 hrs.

Also known as: VePesid, Etopophos

Participants with newly-diagnosed HR-Neuroblastoma

Carboplatin DRUG

Administration of ICE - cycle 2 Days 1-5: Ifosfamide 1500 mg/m2/day (50 mg/kg/day if weight is \<10 kg), IV over 6 hrs. Mesna 1500 mg/m2/day, by 24-hr IV infusion, starting with the ifosfamide infusion. Days 1-2: Carboplatin 400 mg/m2/day (13.3 mg/kg/day if weight is \<10 kg), IV over 1 hr. Days 1-5: Etoposide 100 mg/m2/day (3.3. mg/kg/day if weight is \<10 kg), IV over 2 hrs.

Also known as: Paraplatin

Participants with newly-diagnosed HR-Neuroblastoma

Mesna DRUG

Administration of CTV - cycles 1 and 4 Mesna 70 mg/kg (2100 mg/m2/day for patients \>10 years old) , by 24-hr IV infusion, starting with the cyclophosphamide infusion. Administration of ICE - cycle 2 Mesna 1500 mg/m2/day, by 24-hr IV infusion, starting with the ifosfamide infusion. Administration of CDV - cycle 3 Mesna 70 mg/kg ((2100 mg/m2/day for patients \>10 years old), by 24-hr IV infusion, starting with the cyclophosphamide infusion.

Also known as: Mesnex

Participants with newly-diagnosed HR-Neuroblastoma

Eligibility Criteria

• Age: 1 Year - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of NB as defined by histopathology (confirmed by the MSK Department of Pathology), BM metastases plus high urine catecholamine levels, or positivity in MIBG scan.
• HR-NB, defined as MYCN-amplified stage 2/3/4/4S at any age and stage 4 in patients \>18 months old.
• No more than one prior cycle of chemotherapy.
• Age \<19 years old.
• Signed informed consent indicating awareness of the investigational nature of this treatment.

You may not qualify if:

• Severe dysfunction of major organs, i.e., renal, cardiac, hepatic, neurologic, pulmonary, hematologic, or gastrointestinal toxicity ≥ grade 3.
• Inability to comply with protocol requirements.
• Pregnancy is not an issue because all patients will be pre-adolescents.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neuroblastoma; Neoplasms

Interventions

Cyclophosphamide; Topotecan; Vincristine; Doxorubicin; Ifosfamide; Etoposide; etoposide phosphate; Carboplatin; Mesna

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Oxazines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Coordination Complexes; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Brian Kushner, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 1, 2021
• Study Start: June 22, 2021
• Primary Completion (Estimated): June 22, 2026
• Study Completion (Estimated): June 22, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)