Health TrialsbyHealthPanel

Pediatric Precision Laboratory Advanced Neuroblastoma Therapy

ConditionNeuroblastoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeUp to 22
SponsorGiselle Sholler

About this trial

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 Newly Diagnosed High-Risk Neuroblastoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must be age ≤ 21 years at initial diagnosis

Participants must not have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology.

Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.

Ability to tolerate PBSC collection: No known contraindication to PBSC collection. Examples of contraindications would include a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.

Disqualifiers

Participants who are 12-18 months of age with INSS Stage 4 and all stage 3 participants 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.

Participants receiving any investigational drug concurrently.

Participants 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 participant's ability to sign or the legal guardian's ability to sign the informed consent, and participant's ability to cooperate and participate in the study

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ceritinib

    Drug

    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.

  • dasatinib

    Drug

    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.

  • sorafenib

    Drug

    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.

  • vorinostat

    Drug

    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.

  • DFMO

    Drug

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

Treatment groups

500 Participants
are divided into 2 treatment groups
Group A: Standard Immunotherapy without DFMOActive comparator 4 interventions
Group B: Standard Immunotherapy with DFMOActive comparator 5 interventions

Trial outcomes

Primary outcomes

1

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)

Time frame
Up to 8 years
2

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.

Time frame
2 years
3

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.

Time frame
2 years

Secondary outcomes

1

Number of days that subjects remain alive

To measure the response of treatments chosen based on: * Overall response rate (ORR) after induction therapy * Overall survival (OS)

Time frame
3 years plus 5 years follow up
2

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.

To measure the response of treatments chosen based on: • Overall response rate (ORR) after induction therapy

Time frame
Up to 8 years
3

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

To compare toxicity effects of difluoromethylornithine (DFMO) in combination with anti-GD2 immunotherapy and isotretinoin versus anti-GD2 immunotherapy and isotretinoin alone.

Time frame
3 years
4

Amount of pain medicine required by Arm A versus Arm B

To compare level of pain medicine needed during immunotherapy in patients receiving difluoromethylornithine (DFMO) in combination with anti-GD2 immunotherapy and Isotretinoin versus those receiving anti-GD2 immunotherapy and isotretinoin alone.

Time frame
3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Giselle Sholler

Lead sponsor

Milton S. Hershey Medical Center

Sponsor institution

Dell, Inc.

Collaborator

Beat NB Cancer Foundation

Collaborator

K C Pharmaceuticals Inc.

Collaborator

Team Parker for Life

Collaborator

Source ClinicalTrials.gov
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