Next Generation Personalized Neuroblastoma Therapy

Summary

The purpose of this research study is to match genomic aberrations in tumor cells at time of relapse to rationally designed combinations of molecularly targeted agents. This study will be done in two parts:

Part I: Tumor will be accessed at study entry via a biopsy and subjected to deep sequencing to identify protocol-specified biomarkers for therapy assignment.

Part II: If the tumor contains a genetic change defined by the study as being actionable, and other criteria are met, participants will be assigned to therapy based upon the genetic changes identified in the tumor biopsy.

Conditions

• Neuroblastoma
• Cancer

Interventions

PROCEDURE

Biopsy

Needle or incisional tumor biopsy

GENETIC

Next Generation Sequencing

Tumor tissue will be sent to Foundation Medicine laboratory for molecular profiling.

PROCEDURE

Tumor Scans

Participants will undergo different types of scans to look at your tumor. These scans include CT (computerized tomography), MIBG (meta-iodobenzylguanidine) PET (positron emission tomography), and MRI (magnetic resonance imaging). Participants may have more than one type of scan.

PROCEDURE

Bone marrow Tests

Participants will have needles inserted through their hip bone to remove fluid from inside the bone marrow. This test determines if participants have tumor in the bone marrow.

OTHER

Physical Exam

The exam includes taking participant weight, height, blood pressure, heart rate and respiratory rate and performing a examination of the participants body. The investigators may also check the participants vision with an eye chart.

OTHER

Eye Exam

Participants will have their eyes will be evaluated using different instruments. Participants will also be asked to read an eye chart. The exams will take about 15 minutes.

OTHER

Labs

Standard blood tests will be done to measure different types of blood cells, to measure the amount of certain substances, and tests to check how well liver and kidneys are working. When possible, the investigators will take blood from the participants central line. If this is not possible, the investigators will take blood from a vein in the participants arm. First, the investigators will put some cream on the skin so that drawing blood will not be painful. Then the investigators will put a thin needle into the vein to draw the blood.

OTHER

Pregnancy Test

If the participant is 11 years old or older or has already started having periods, the participant will be asked to take a pregnancy test before starting this study. The results will be shared with the participant but not with the participants' parent(s). We strongly encourage the participant to share the results with the parents. If the participant is found to be pregnant, the participant will not be able to continue participation in the study. About 1 teaspoon of blood (or urine if a urine test) will be needed.

BEHAVIORAL

Interviews

A team member will take the participant's medical history, along with a listing of any medications that are being taken. Throughout the study, participants will be asked to report if they think that anything bad has happened as a result of the study.

OTHER

ECG

This is a test of electrical activity of the heart. The investigators will put electrodes (sticky pads attached to wires) on the participant's chest, arms and legs. The electrocardiogram (ECG) will not be uncomfortable, but the participant will have to lie still. It does not hurt and takes about 15 minutes.

OTHER

Echocardiogram

The participant will have an Echocardiogram (ECHO), an ultrasound of the heart, taken to assess heart function. The investigators will put some gel on the skin and use a machine to take pictures of the heart.

DRUG

Ribociclib

Participants will take ribociclib once per day orally for Days 1-21 of a 28-day cycle.

DRUG

Ceritinib

Participants will take ceritinib once per day orally for 28 days of a 28-day cycle.

Sponsors & Collaborators

• Novartis Pharmaceuticals

  collaborator INDUSTRY

• Foundation Medicine

  collaborator INDUSTRY

• Yael P Mosse

  lead OTHER

Principal Investigators

• Yael P Mossé, MD · Children's Hospital of Philadelphia, The University of Pennsylvania

• John M Maris, MD · Children's Hospital of Philadelphia, The University of Pennsylvania

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-07-31

Primary Completion

2022-08-31

Completion

2022-08-31

Countries

• United States

Study Locations