LDK378 in children with malignancies that have ALK alteration
Research type
Research Study
Full title
A phase 1 open label dose escalation study of LDK378 in paediatric patients with malignancies that have a genetic alteration in anaplastic lymphoma kinase
IRAS ID
123922
Contact name
Pamela Kearns
Contact email
Sponsor organisation
Novartis Pharma Services
Eudract number
2012-002074-31
Clinicaltrials.gov Identifier
Research summary
The ALK gene was first described in anaplastic large cell lymphoma (ALCL); it was
identified as the t(2;5)(p23;Q35)translocation, and is found in approximately half of patients with ALCL, and a majority of paediatric ALCL cases. Half of inflammatory myofibroblastic tumours (IMT), a rare soft tissue sarcoma most commonly found in children,harbour genetic alterations of ALK. Increased ALK protein expression and increased ALK gene copy number have also been described recently in 50%-80% of rhabdomyosarcomas. ALK mutations and amplification are also present in approximately 15% of children with neuroblastoma, the most frequent paediatric solid extracranial tumour.
LDK378 is a novel inhibitor of ALK that is active in a broad range of ALK-activated
tumour models, including models driven by mutated versions of ALK known to be
resistant to crizotinib, and by ALK gene amplification.
The primary purpose of this study is to determine the maximum tolerated dose (MTD)
and/or recommended dose for expansion (RDE) in paediatric patients, and to find
a clinical dose to be used in any future paediatric studies. This study will also assess the safety, tolerability, PK and preliminary evidence of antitumou activity of LDK378 in paediatric patients with neuroblastoma, and other ALK-activated tumours.REC name
London - City & East Research Ethics Committee
REC reference
13/LO/0727
Date of REC Opinion
24 Jul 2013
REC opinion
Further Information Favourable Opinion