Eurosarc Trial of Linsitinib in Advanced Ewing Sarcoma (LINES)
Relapsed Ewing Sarcoma
Refractory Ewing Sarcoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Linsitinib (Anti-IGF-1R/IR) in Patients With Relapsed and/or Refractory Ewing Sarcoma|
- To determine the pharmacodynamic effect of Linsitinib in the tumour (FDG uptake (SUV) responses in ES tumours using functional imaging 18FDG-PET-CT) [ Time Frame: Pre- and Post- dose responses following 1 cycle (21 days) of treatment ] [ Designated as safety issue: No ]Pharmacodynamic FDG uptake (SUV) responses in ES tumours using functional imaging 18FDG-PET-CT and repeat post treatment biopsies to establish biomarker responses in tumour biopsies
- To evaluate the safety and tolerability of Linsitinib (adverse events and laboratory abnormalities (CTCAE v4.0 grade, timing, seriousness and relatedness) [ Time Frame: Following 6 cycles of treatment (up to 6 months) ] [ Designated as safety issue: Yes ]Quantity and severity of
- Clinical outcome (PFS, DSS, ORR) [ Time Frame: Duration of study (up to 18 months) ] [ Designated as safety issue: No ]
To determine the clinical outcome through assessment of
- Progression free survival; where length of survival is defined in whole days as the time from entry into the study until Ewing sarcoma progression or death from any cause.
- Disease specific survival; where length of survival is defined in whole days as the time from entry into the study until death from Ewing sarcoma.
- Objective responses (RECIST)
- Pharmacokinetics assays of following linsitinib treatment (Plasma concentrations of linsitinib) [ Time Frame: Duration of study treatment (up to 18 months) ] [ Designated as safety issue: No ]Plasma concentrations of linsitinib will be measured and appropriate pharmacokinetic analysis will be performed
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
An important development in ES has been the identification of IGF-1R pathway dependency. The reasons for the remarkable single agent efficacy observed in a small subset of patients remains unknown, as is the relative lack of efficacy in the majority of patients. There may be heterogeneity in response due to partial signal pathway inhibition at the tumour level, inherent resistance in ES cells or the presence of alternative pathway activation through IR-A receptor signalling.
Here we aim to establish pharmacodynamic responses in ES tumours using functional imaging 18FDG-PET-CT and repeat post treatment biopsy for biomarker responses, toxicity and clinical outcome to the dual anti-IGF-1R/IR kinase blocking single agent linsitinib.
This is a single arm phase 2 study utilising adaptive Bayesian analysis. Approximately 40 patients will be recruited the national bone sarcoma centre in 5 EU countries over 18 months.
Eligible patients will take 4x 150 mg tablets once a day, days 1-3 of the week followed by 4 days off - repeated for 3 weeks = one treatment cycle. Patients can remain on treatment for as long as they gain clinical benefit.
The primary objectives are to determine the effect of linsitinib on the patient's tumours in terms of changes in biomarker and PET scans and to establish the safety of the trial drug (linsitinib) in Ewing sarcoma at the dose and treatment schedule being used in the trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02546544
|Contact: Ade Faleti||01865 firstname.lastname@example.org|
|Universitè Lyon 1 Claude Bernard||Not yet recruiting|
|Contact: Jean-Yves Blay, MD, PhD 35 (0) 478782757 email@example.com|
|Principal Investigator: Jean-Yves Blay, MD, PhD|
|Pediatric Hematology and Oncology, University Hospital Münster||Not yet recruiting|
|Münster, Germany, 48149|
|Contact: Uta Dirksen 49 (0)251 834 7742 Uta.Dirksen@ukmuenster.de|
|Sub-Investigator: Herbert Jürgens, MD|
|Principal Investigator: Uta Dirksen, MD|
|Istituti Ortopedici Rizzoli||Recruiting|
|Bologna, Italy, 40136|
|Contact: Stefano Ferrari, MD 39-051-636 61 99 firstname.lastname@example.org|
|Contact: Piero Picci, MD email@example.com|
|Principal Investigator: Stefano Ferrari, MD|
|Sub-Investigator: Piero Picci, MD|
|Department of Clinical Oncology, Leiden University Medical Center||Recruiting|
|Leiden, Postzone K1-P, Netherlands, P.O. Box 9600|
|Contact: Hans Gelderblom, M.D., Ph.D. 31(0)71-5263486 firstname.lastname@example.org|
|Contact: Wendy van Andel 31(0)71-5263486 W.van_Andel@lumc.nl|
|Principal Investigator: Hans Gelderblom, M.D. Ph.D.|
|Oxford University Hospitals NHS Foundation Trust||Recruiting|
|Oxford, United Kingdom, OX3 7LE|
|Principal Investigator: Bass Hassan, MD|
|Sub-Investigator: Sarah Pratap, MD|
|Principal Investigator:||Andrew B Hassan, BSc(Hon) BMBCh MRCP DPhil FRCP||University of Oxford|