Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Hematinics

Antineoplastic Agents

Amino Acids

Morphine

Liver Extracts

3-Iodobenzylguanidine

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

All participants with relapsed or refractory neuroblastoma will have a tumor biopsy to identify genetic mutations. There is no drug given in this arm of the trial.

Qualified participants whose tumors show certain mutations in the anaplastic lymphoma kinase (ALK) pathway (based on genetic sequencing results) will receive a combination therapy of ceritinib and ribociclib, to be administered orally in 28-day cycles.

Two different doses of ceritinib and three different doses of ribociclib will be evaluated. Once the investigators have identified the highest safe dose of both drugs that can be given at the same time, additional participants will be enrolled in the study at this dose level.

It is possible that if starting at a lower dose, participants may take a higher dose once that dose has been deemed safe.

Biopsy

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

Next Generation Sequencing

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.

Tumor Scans

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.

Bone marrow Tests

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.

Physical 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.

Eye Exam

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.

Labs

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.

Pregnancy Test

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.

Interviews

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.

The participant will have 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.

Echocardiogram

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

Ribociclib

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

Yael P Mossé, MD

John M Maris, MD

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.

Next Generation Personalized Neuroblastoma Therapy

Next Generation Personalized Neuroblastoma Therapy (The NEPENTHE Trial)

The primary variable is the incidence of dose limiting toxicities (DLTs) during the first 28 days of therapy

Area under the plasma concentration time-curve from zero to the last measured concentration

To describe whether the assigned targeted therapy can mediate anti-tumor effects in subjects with relapsed or refractory high-risk neuroblastoma within the context of a phase 1/phase1b biomarker-driven trial. Percentage of patients with objective response will be according to the International Neuroblastoma Response Criteria.

Neuroblastomas undergo substantial mutational evolution during therapy, and relapsed disease is more likely to be driven by a targetable oncogenic pathway. Genomic alterations measured by next-generation sequencing at time of disease progression will be characterized and reported in a descriptive manner.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Next Generation Personalized Neuroblastoma Therapy	NCT02780128	Neuroblastoma Cancer	Biopsy Next Generation... Tumor Scans Bone marrow Tes... Physical Exam Eye Exam Labs Pregnancy Test Interviews ECG Echocardiogram Ribociclib Ceritinib	1 Year - 21 Years	Children's Hospital of Philadelphia
Next Generation Personalized Neuroblastoma Therapy	NCT02780128	Neuroblastoma Cancer	Biopsy Next Generation... Tumor Scans Bone marrow Tes... Physical Exam Eye Exam Labs Pregnancy Test Interviews ECG Echocardiogram Ribociclib Ceritinib	1 Year - 21 Years	Children's Hospital of Philadelphia

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