Back to resultsA Study of N9 Chemotherapy in Children With Neuroblastoma
Primary Purpose
Neuroblastoma, Pediatric Cancer
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Topotecan
Vincristine
Doxorubicin
Ifosfamide
Etoposide
Carboplatin
Mesna
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring HR-NB, Neuroblastoma, pediatric cancer, 21-228, Memorial Sloan Cancer Center
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 >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.
Sites / Locations
- Memorial Sloan Kettering Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Participants with newly-diagnosed HR-Neuroblastoma
Arm Description
This pilot study of N9 as induction chemotherapy will enroll 15 patients with newly-diagnosed HR-NB.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT04947501
First Posted
June 23, 2021
Last Updated
August 1, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT04947501
Brief Title
A Study of N9 Chemotherapy in Children With Neuroblastoma
Official Title
N9: Pilot Study of Novel Shortened Induction Chemotherapy for High-Risk Neuroblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 22, 2021 (Actual)
Primary Completion Date
June 22, 2025 (Anticipated)
Study Completion Date
June 22, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Pediatric Cancer
Keywords
HR-NB, Neuroblastoma, pediatric cancer, 21-228, Memorial Sloan Cancer Center
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Participants with newly-diagnosed HR-Neuroblastoma
Arm Type
Experimental
Arm Description
This pilot study of N9 as induction chemotherapy will enroll 15 patients with newly-diagnosed HR-NB.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
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
Intervention Name(s)
Topotecan
Other Intervention Name(s)
Hycamtin
Intervention Description
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
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin
Intervention Description
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
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
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
Intervention Name(s)
Ifosfamide
Other Intervention Name(s)
Isophosphamide
Intervention Description
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
Intervention Name(s)
Etoposide
Other Intervention Name(s)
VePesid, Etopophos
Intervention Description
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
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
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
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assess safety of the N9 regimen in participants with HR-NB through toxicity assessment
Description
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
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
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 >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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brian Kushner, MD
Phone
1-833-MSK-KIDS
Email
kushnerb@MSKCC.ORG
First Name & Middle Initial & Last Name or Official Title & Degree
Shakeel Modak, MD
Phone
1-833-MSK-KIDS
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Kushner, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian Kushner, MD
Phone
833-675-5491
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
A Study of N9 Chemotherapy in Children With Neuroblastoma
We'll reach out to this number within 24 hrs