A Study of N9 Chemotherapy in Children With Neuroblastoma

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04947501
Collaborator
(none)
15
1
1
24
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Study Details

Study Description

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
N9: Pilot Study of Novel Shortened Induction Chemotherapy for High-Risk Neuroblastoma
Actual Study Start Date :
Jun 22, 2021
Anticipated Primary Completion Date :
Jun 22, 2023
Anticipated Study Completion Date :
Jun 22, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Participants with newly-diagnosed HR-Neuroblastoma

This pilot study of N9 as induction chemotherapy will enroll 15 patients with newly-diagnosed HR-NB.

Drug: 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.
Other Names:
  • Cytoxan
  • 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.
    Other Names:
  • Hycamtin
  • 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.
    Other Names:
  • Oncovin
  • 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.
    Other Names:
  • Adriamycin
  • Drug: Ifosfamide
    Administration of ICE - cycle 2 Days 1-5: Ifosfamide 1500 mg/m2/day, 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, IV over 1 hr. Days 1-5: Etoposide 100 mg/m2/day, IV over 2 hrs.
    Other Names:
  • Isophosphamide
  • Drug: Etoposide
    Administration of ICE - cycle 2 Days 1-5: Ifosfamide 1500 mg/m2/day, 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, IV over 1 hr. Days 1-5: Etoposide 100 mg/m2/day, IV over 2 hrs.
    Other Names:
  • VePesid
  • Etopophos
  • Drug: Carboplatin
    Administration of ICE - cycle 2 Days 1-5: Ifosfamide 1500 mg/m2/day, 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, IV over 1 hr. Days 1-5: Etoposide 100 mg/m2/day, IV over 2 hrs.
    Other Names:
  • Paraplatin
  • 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.
    Other Names:
  • Mesnex
  • Outcome Measures

    Primary Outcome Measures

    1. Assess safety of the N9 regimen in participants with HR-NB through toxicity assessment [16 weeks]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 13 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 >1 year to <13 years old.

    • Organ function requirements:

    Adequate renal function defined as:

    Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m^2 or A serum creatinine based on age/sex as follows:

    Age: 1 to < 2 years Maximum Serum Creatinine (mg/dL): Male, 0.6; Female, 0.6 Age: 2 to < 6 years Maximum Serum Creatinine (mg/dL): Male, 0.8; Female, 0.8 Age: 6 to ≤ 10 years Maximum Serum Creatinine (mg/dL): Male, 1; Female, 1

    The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control.

    Adequate liver function defined as:

    Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and serum alanine aminotransferase (ALT) < 10 x ULN.

    Adequate cardiac function defined as:

    Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of > 50% by echocardiogram or radionuclide angiogram.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Memorial Sloan Kettering Cancer Center New York New York United States 10065

    Sponsors and Collaborators

    • Memorial Sloan Kettering Cancer Center

    Investigators

    • Principal Investigator: Brian Kushner, MD, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Memorial Sloan Kettering Cancer Center
    ClinicalTrials.gov Identifier:
    NCT04947501
    Other Study ID Numbers:
    • 21-228
    First Posted:
    Jul 1, 2021
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Memorial Sloan Kettering Cancer Center
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 12, 2022