Next Generation Personalized Neuroblastoma Therapy

Next Generation Personalized Neuroblastoma Therapy (The NEPENTHE Trial)

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.

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.