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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06172296




Registration number
NCT06172296
Ethics application status
Date submitted
13/12/2023
Date registered
15/12/2023

Titles & IDs
Public title
Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
Scientific title
A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma
Secondary ID [1] 0 0
NCI-2023-08530
Secondary ID [2] 0 0
NCI-2023-08530
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ganglioneuroblastoma, Nodular 0 0
Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Marrow Aspiration
Treatment: Surgery - Bone Marrow Biopsy
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Other - Dinutuximab
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Etoposide
Treatment: Surgery - FDG-Positron Emission Tomography and Computed Tomography Scan
Treatment: Surgery - Hematopoietic Cell Transplantation
Treatment: Drugs - Irinotecan
Treatment: Drugs - Isotretinoin
Treatment: Surgery - Leukapheresis
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Drugs - Melphalan
Treatment: Other - Radiation Therapy
Treatment: Surgery - Radionuclide Imaging
Other interventions - Survey Administration
Treatment: Drugs - Temozolomide
Treatment: Drugs - Thiotepa
Treatment: Drugs - Topotecan
Treatment: Surgery - Tumor Resection
Treatment: Drugs - Vincristine

Active comparator: Arm A (SOC treatment) - See detailed description

Experimental: Arm B (Dinutuximab in induction) - See detailed description


Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Bone Marrow Aspiration
Undergo bone marrow aspiration

Treatment: Surgery: Bone Marrow Biopsy
Undergo bone marrow biopsy

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Cisplatin
Given IV

Treatment: Surgery: Computed Tomography
Undergo CT scan

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Other: Dinutuximab
Given IV

Treatment: Drugs: Doxorubicin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Surgery: FDG-Positron Emission Tomography and Computed Tomography Scan
Undergo FDG PET

Treatment: Surgery: Hematopoietic Cell Transplantation
Undergo stem cell infusion

Treatment: Drugs: Irinotecan
Given IV

Treatment: Drugs: Isotretinoin
Given PO

Treatment: Surgery: Leukapheresis
Undergo apheresis

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Drugs: Melphalan
Given IV

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Surgery: Radionuclide Imaging
Undergo I-MIBG scan

Other interventions: Survey Administration
Ancillary studies

Treatment: Drugs: Temozolomide
Given PO or via NG or G tube

Treatment: Drugs: Thiotepa
Given IV

Treatment: Drugs: Topotecan
Given IV

Treatment: Surgery: Tumor Resection
Undergo tumor resection surgery

Treatment: Drugs: Vincristine
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Intervention code [4] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event free survival (EFS)
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
End of Induction (EOI) response rate
Timepoint [1] 0 0
From randomization to end of extended Induction, up to 12 months
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Incidence of adverse events
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
GD2 expression
Timepoint [4] 0 0
Up to 12 months

Eligibility
Key inclusion criteria
* Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
* = 30 years at the time of initial diagnosis with high-risk disease
* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines

* Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:

* Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
* Age = 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
* Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
* Age = 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
* Patients must have a BSA = 0.25 m^2
* No prior anti-cancer therapy except as outlined below:

* Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
* Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria
* Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* A serum creatinine based on age/sex derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the CDC or

* a 24-hour urine creatinine clearance = 70 mL/min/1.73 m^2 or
* a GFR = 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard) Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin = 1.5 x upper limit of normal (ULN) for age
* Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase [ALT]) = 10 x ULN*

* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of = 27% by echocardiogram, or ejection fraction of = 50% by echocardiogram or radionuclide angiogram
* Ability to tolerate Peripheral Blood Stem Cell (PBSC) Collection:

No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Minimum age
No limit
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients who are 365-546 days of age with INRG Stage M and MYCN non amplified NBL, irrespective of additional biologic features
* Patients = 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
* Patients with known bone marrow failure syndromes
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, food and drug administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
478
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
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District of Columbia
Country [9] 0 0
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kentucky
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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New Hampshire
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
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Texas
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Virginia
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Washington
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Wisconsin
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Canada
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Manitoba
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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New Zealand
State/province [41] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sara M Federico
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://grants.nih.gov/policy/sharing.htm


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06172296