Next Generation Personalized Neuroblastoma Therapy (NEPENTHE)

Yael P Mosse

Status and phase: Terminated; Phase 1

Conditions: Neuroblastoma; Cancer

Treatments: Drug: Ceritinib; Procedure: Biopsy; Genetic: Next Generation Sequencing; Other: Labs; Behavioral: Interviews; Other: ECG; Procedure: Tumor Scans; Other: Eye Exam; Drug: Ribociclib; Other: Physical Exam; Other: Pregnancy Test; Other: Echocardiogram; Procedure: Bone marrow Tests

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02780128

14-011071

Details and patient eligibility

About

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.

Enrollment: 66 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged ≥1 years to ≤ 21 years
• Relapsed or refractory neuroblastoma
• A sufficient interval between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies) and enrollment in this study, to allow recovery from the acute toxic effects of all prior anti-cancer therapy. Please contact site for specific details
• Adequate bone marrow function (bone marrow may be involved with tumor. Contact site for specific details)
• Adequate renal function, defined as Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2 OR serum creatinine based on age/gender normal (contact site for details)
• Adequate liver function, defined as total serum bilirubin ≤ 1.5 times the upper limit of normal AND alanine transaminase (ALT) ≤ 110 U/L.
• Adequate cardiac function, defined as corrected QT interval (QTc) ≤ 480 msec AND shortening fraction > 27%
• Males and females who are sexually active must agree to use effective contraception during and for 3 months after treatment

Exclusion criteria

• Subjects taking certain drugs or herbal medications that impact drug metabolism and/or cardiac function that cannot be discontinued (contact site for details).
• Subjects with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (contact site for details)
• Other concomitant therapies:
• Corticosteroids initiated for tumor therapy within 7 days prior to study enrollment
• Other anti-cancer agents
• Other investigational drugs
• Hematological growth factors
• Radiation therapy
• Subjects < 0.5m2
• Pregnant or lactating females
• Sexually active males unless they use a condom during intercourse while taking study drug/s and for 3 months after study drug discontinuation and thus do not attempt to father a child in this period.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 2 patient groups

Molecular Analysis

Other group

Description:

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.

Treatment:

Other: Physical Exam

Behavioral: Interviews

Other: Pregnancy Test

Other: Labs

Genetic: Next Generation Sequencing

Procedure: Biopsy

Procedure: Tumor Scans

Group 1: ALK

Experimental group

Description:

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.

Treatment:

Other: Echocardiogram

Procedure: Bone marrow Tests

Drug: Ribociclib

Other: Physical Exam

Other: Eye Exam

Behavioral: Interviews

Other: Pregnancy Test

Other: ECG

Other: Labs

Drug: Ceritinib

Procedure: Tumor Scans