Next Generation Personalized Neuroblastoma Therapy

Phase 1TerminatedNCT02780128

Yael P Mosse66 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neuroblastoma Cancer

Interventions

BiopsyPROCEDURE

Needle or incisional tumor biopsy

Next Generation SequencingGENETIC

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

Tumor ScansPROCEDURE

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.

Eligibility

Sex: ALLMin age: 1 YearMax age: 21 Years

Medical Language ↔ Plain English

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.

Locations (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Incidence of dose limiting toxicities when combining ceritinib with ribociclib

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

Time frame: At the end of Cycle 1 (each cycle is 28 days)

Area under the curve from time zero to last quantifiable concentration

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

Time frame: At the end of Cycle 1 (each cycle is 28 days)

Percentage of patients with overall objective response

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.

Time frame: 2 years

Secondary Outcomes

Cataloguing of genomic alterations identified from biopsies performed at time of relapse in patients with relapsed or refractory neuroblastoma

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.

Time frame: 3 years

Data from ClinicalTrials.gov

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