LOXO - 101

Author: Julia Dobke, erstellt am: 2018/02/14, Last modification: 2018/09/12

LOXO - 101 A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors
Disease Solid tumors or CNS tumors
Type Multicenter, open-label, Phase I/II (Germany only phase II)
Problem / Objectives

Primary objectives

Phase I
-To characterize the PK properties of larotrectinib in pediatric patients with advanced solid or primary CNS tumors
-To identify the MTD and/or the appropriate dose of larotrectinib for further clinical investigation in this patient population
-To describe the antitumor activity of larotrectinib
-To describe pain and health related quality of life (HRQoL)

Phase II
-To determine the ORR based on the treating Investigator’s response assessment using RECIST 1.1 or RANO criteria, as appropriate to tumor type

Secondary objectives

Phase I:
-To evaluate potential biomarkers of response and resistance to larotrectinib

Phase II
-To determine the ORR based on the treating Investigator’s response assessment using RECIST 1.1 or RANO criteria, as appropriate to tumor type
-To evaluate the duration of response (DOR) in patients with best overall response of
-CR or PR as determined by 1) an independent radiology review committee and 2) the treating Investigator
-To estimate the proportion of patients that has any tumor regression as a best response
-To evaluate the duration of progression-free survival (PFS) following initiation of larotrectinib
-To evaluate the duration of OS following initiation of larotrectinib
-To asess the safety profile and tolerability of larotrectinib

Inclusion Criteria
  • Children from 0 to 21 with a locally advanced or metastatic infantile fibrosarcoma with a positive ETS variant gene 6 (ETV6) break-apart fluorescence in situ hybridization (FISH) or other appropriate molecular analysis.
  • 0 through 21 years with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion
  • at least one measurable lesion as defined by RECIST or RANO
  • Karnofsky or Lansky > 50
Exclusion Criteria
  • Major surgery within 14 days (2 weeks) prior to C1D1…
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QT interval
Recruitment Phase I: 54 patients, Phase 2 30 patients
Status open
EudraCT 2016-003498-16
Entry Study Register ClinicalTrials.gov: NCTNCT02637687
Principal Investigator Prof. Stefan Bielack
E-Mail s.bielack@klinikum-stuttgart.de

Principal Investigator

Prof. Dr. med. Stefan Bielack Klinikum Stuttgart - Olgahospital Zentrum für Kinder-, Jugend- und Frauenmedizin, Pädiatrie 5 (Onkologie, Hämatologie, Immunologie) Kriegsbergstr. 62 70174 Stuttgart Telefon +49 (711) 278 72460 Fax +49 (711) 278 72462 coss@klinikum-stuttgart.de

Secondary Investigator

Cornelis van Tilburg Hopp-Kindertumorzentrum am NCT Heidelberg Klinik für Kinderheilkunde III Onkologie, Hämatologie, Immunologie Telefon +49 (6221) 56 37082 Fax +49 (6221) 56 6491 zipo@kitz-heidelberg.de

Participants Stuttgart, Heidelberg, Berlin
Sponsoring LOXO Oncology Inc, USA