NCT02559778

Brief Summary

A prospective open label, multicenter study to evaluate the feasibility and acute toxicity of using molecularly guided therapy in combination with standard therapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
500

participants targeted

Target at P75+ for phase_2

Timeline
114mo left

Started Sep 2015

Longer than P75 for phase_2

Geographic Reach
2 countries

28 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress53%
Sep 2015Sep 2035

Study Start

First participant enrolled

September 1, 2015

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

September 22, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 24, 2015

Completed
14.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2030

Expected
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2035

Last Updated

April 28, 2026

Status Verified

April 1, 2026

Enrollment Period

15 years

First QC Date

September 22, 2015

Last Update Submit

April 24, 2026

Conditions

Outcome Measures

Primary Outcomes (3)

  • Number of days from start of therapy to date of first relapse

    To measure the response of treatments chosen based on: • Event free survival (EFS)

    Up to 8 years

  • Number of subjects that have a targeted agent chosen for treatment.

    At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as: 1. Subject has a targeted agent identified 2. Receives 75% of dosing of medications while on study protocol during cycles 3-6 3. Subject is not removed from study due to targeted agent drug related toxicity.

    2 years

  • Number of subjects that receive 75% of dosing of medications while on study protocol during cycles 3-6.

    At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as: 1. Subject has a targeted agent identified 2. Receives 75% of dosing of medications while on study protocol during cycles 3-6 3. Subject is not removed from study due to targeted agent drug related toxicity.

    2 years

Secondary Outcomes (5)

  • Number of days that subjects remain alive

    3 years plus 5 years follow up

  • Overall Response Rate (ORR) of Participants by the presence of radiologically assessable disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans.

    Up to 8 years

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    3 years

  • Amount of pain medicine required by Arm A versus Arm B

    3 years

  • Number of subjects required to go off therapy due to treatment-related adverse events as assessed by CTCAE v4.0.

    1 year

Study Arms (2)

Standard Immunotherapy without DFMO

ACTIVE COMPARATOR

One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days.

Drug: CeritinibDrug: dasatinibDrug: sorafenibDrug: vorinostat

Standard Immunotherapy with DFMO

ACTIVE COMPARATOR

One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days.

Drug: CeritinibDrug: dasatinibDrug: sorafenibDrug: vorinostatDrug: DFMO

Interventions

One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.

Also known as: Zykadia
Standard Immunotherapy with DFMOStandard Immunotherapy without DFMO

One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.

Also known as: Sprycel
Standard Immunotherapy with DFMOStandard Immunotherapy without DFMO

One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.

Also known as: Nexavar
Standard Immunotherapy with DFMOStandard Immunotherapy without DFMO

One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.

Also known as: ZOLINZA
Standard Immunotherapy with DFMOStandard Immunotherapy without DFMO
DFMODRUG

DFMO will be given to Arm B during immunotherapy and then for 2 years as maintenance to all subjects completing immunotherapy.

Also known as: Eflornithine, α-difluoromethylornithine
Standard Immunotherapy with DFMO

Eligibility Criteria

AgeUp to 22 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may not qualify if:

  • Subjects who are 12-18 months of age with INSS Stage 4 and all stage 3 subjects with favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index \> 1) are not eligible.
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants.
  • Subjects receiving any investigational drug concurrently.
  • Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

University of Alabama/Children's of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

RECRUITING

Nicklaus Children's Miami

Miami, Florida, 33155, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

St. Joseph's Children's Hospital

Tampa, Florida, 33614, United States

RECRUITING

Augusta University Health

Augusta, Georgia, 30912, United States

RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96813, United States

RECRUITING

St. Lukes

Boise, Idaho, 83712, United States

COMPLETED

Advocate Aurora Research Institute

Chicago, Illinois, 60453, United States

COMPLETED

Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine

Louisville, Kentucky, 40202, United States

RECRUITING

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

COMPLETED

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

COMPLETED

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

RECRUITING

Randall Children's Hospital

Portland, Oregon, 97227, United States

RECRUITING

Penn State Milton S. Hershey Medical Center and Children's Hospital

Hershey, Pennsylvania, 17033, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Dell Children's Blood and Cancer Center

Austin, Texas, 78723, United States

RECRUITING

Children's Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, AB T3B 6A8, Canada

RECRUITING

CHU Sainte-Justine

Montreal, Quebec, QC H3S 2G4, Canada

RECRUITING

CHUQ

Québec, Quebec, QC G1V 4W6, Canada

RECRUITING

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, QC J1H 5H3, Canada

RECRUITING

Related Links

MeSH Terms

Conditions

Neuroblastoma

Interventions

ceritinibDasatinibSorafenibVorinostatEflornithine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidinesPhenylurea CompoundsUreaAmidesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicPyridinesAnilidesAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsOrnithineAmino Acids, BasicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Diamino

Study Officials

  • Giselle Sholler, MD

    Beat Childhood Cancer

    STUDY CHAIR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Beat Childhood Cancer Chair

Study Record Dates

First Submitted

September 22, 2015

First Posted

September 24, 2015

Study Start

September 1, 2015

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

September 1, 2035

Last Updated

April 28, 2026

Record last verified: 2026-04

Locations