A Study of N9 Chemotherapy in Children With Neuroblastoma

NCT ID: NCT04947501

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-22
• Study Completion Date: 2026-06-22

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants with newly-diagnosed HR-Neuroblastoma

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.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: 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.

Topotecan

Intervention Type: 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.

Vincristine

Intervention Type: 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.

Doxorubicin

Intervention Type: 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.

Ifosfamide

Intervention Type: 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.

Etoposide

Intervention Type: 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.

Carboplatin

Intervention Type: 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.

Mesna

Intervention Type: 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.

Interventions

Cyclophosphamide

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.

Intervention Type: DRUG

Topotecan

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.

Intervention Type: DRUG

Vincristine

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.

Intervention Type: DRUG

Doxorubicin

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.

Intervention Type: DRUG

Ifosfamide

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.

Intervention Type: DRUG

Etoposide

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.

Intervention Type: DRUG

Carboplatin

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.

Intervention Type: DRUG

Mesna

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.

Intervention Type: DRUG

Other Intervention Names

Cytoxan; Hycamtin; Oncovin; Adriamycin; Isophosphamide; VePesid; Etopophos; Paraplatin; Mesnex

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Kushner, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

21-228

Identifier Type: -

Identifier Source: org_study_id