A Study of N9 Chemotherapy in Children With Neuroblastoma
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).
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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:
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:
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:
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:
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:
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:
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:
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Outcome Measures
Primary Outcome Measures
- 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
Inclusion Criteria:
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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.
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HR-NB, defined as MYCN-amplified stage 2/3/4/4S at any age and stage 4 in patients >18 months old.
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No more than one prior cycle of chemotherapy.
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Age >1 year to <13 years old.
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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:
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Severe dysfunction of major organs, i.e., renal, cardiac, hepatic, neurologic, pulmonary, hematologic, or gastrointestinal toxicity ≥ grade 3.
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Inability to comply with protocol requirements.
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Pregnancy is not an issue because all patients will be pre-adolescents.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- 21-228