NANT/Pfizer Lorlatinib Study
Research type
Research Study
Full title
NANT 2015-02: PHASE 1 STUDY OF LORLATANIB (PF-06463922), AN ORAL SMALL MOLECULE INHIBITOR OF ALK/ROS1, FOR PATIENTS WITH RELAPSED OR REFRACTORY NEUROBLASTOMA
IRAS ID
232769
Contact name
Lynley Vanessa Marshall
Contact email
Sponsor organisation
NANT Operations Centre
Eudract number
2017-000640-18
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 9 months, 1 days
Research summary
Neuroblastomas are tumours which arise from the sympathetic nervous system and are the most common malignancy in the first year of life. Around 50% are metastatic at diagnosis and many patients are either resistant to initial treatments or relapse quickly. Outcomes for these patients remains poor. It is therefore necessary for novel approaches in treatment to be trialled to improve outcome. The recent discovery that specific changes in the ALK gene occur in neuroblastoma and can be targeted with a variety of ALK-inhibitors developed for treatment of adult cancers is critical because we now have a series of known ALK-drugs that we can test in children. We have found that Crizotinib, the first ALK drug trialled in neuroblastoma, is ineffective when certain molecular changes are present in ALK. Our research has predicted that Lorlatinib, a 3rd generation, and very potent ALK drug, will be effective for these resistant neuroblastomas. Here we will be testing Lorlatinib in a phase I trial of children or adolescents with relapsed neuroblastoma, to determine the maximum tolerated dose (MTD) of Lorlatinib that is safe in children. Children can have received prior treatment with other ALK inhibitors. Additionally we will genetically test our patients to prove that their tumours have changes in ALK (only patients with tumour that have mutations, amplifications or fusions in ALK will be eligible for treatment), to maximise potential that the drug will be effective. Once the MTD has been identified an expansion cohort of ALK positive patients will be treated in the second phase of the study, on Lorlatinib only or Lorlatinib combined with two commonly used chemotherapy drugs - topotecan and cyclophosphamide.
REC name
London - City & East Research Ethics Committee
REC reference
18/LO/0561
Date of REC Opinion
13 Aug 2018
REC opinion
Further Information Favourable Opinion