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A Study of N9 Chemotherapy in Children With Neuroblastoma

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ClinicalTrials.gov Identifier: NCT04947501
Recruitment Status : Recruiting
First Posted : July 1, 2021
Last Update Posted : August 12, 2021
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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
Neuroblastoma Pediatric Cancer Drug: Cyclophosphamide Drug: Topotecan Drug: Vincristine Drug: Doxorubicin Drug: Ifosfamide Drug: Etoposide Drug: Carboplatin Drug: Mesna Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 22, 2021
Estimated Primary Completion Date : June 22, 2022
Estimated Study Completion Date : June 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Mesnex




Primary Outcome Measures :
  1. Assess safety of the N9 regimen in participants with HR-NB through toxicity assessment [ Time Frame: 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



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Ages Eligible for Study:   1 Year to 13 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 MYCN-nonamplified 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04947501


Contacts
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Contact: Brian Kushner, MD 1-833-MSK-KIDS kushnerb@MSKCC.ORG
Contact: Shakeel Modak, MD 1-833-MSK-KIDS

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Brian Kushner, MD    833-675-5491      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Brian Kushner, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04947501    
Other Study ID Numbers: 21-228
First Posted: July 1, 2021    Key Record Dates
Last Update Posted: August 12, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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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:
HR-NB
Neuroblastoma
pediatric cancer
21-228
Memorial Sloan Cancer Center
Additional relevant MeSH terms:
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Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Ifosfamide
Carboplatin
Doxorubicin
Etoposide
Vincristine
Topotecan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors