NCT02546544

Eurosarc Trial of Linsitinib in Advanced Ewing Sarcoma

Phase II Trial of Linsitinib (Anti-IGF-1R/IR) in Patients With Relapsed and/or Refractory Ewing Sarcoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This is an international, multi-centre, single arm Bayesian designed phase 2 study to identify and determine the safety and activity of anti-IGF-1/IR inhibition in patients with relapsed and/or refractory ESFT. Approximately 40 patients will be recruited from 5-7 European centres. Each patient will be treated with single agent linsitinib, 600 mg orally once a day for days 1-3, 8-10 and 15-17 on a 21 day cycle until disease progression or undue toxicity.

Detailed description

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.

Conditions

• Relapsed Ewing Sarcoma
• Refractory Ewing Sarcoma

Interventions

Type	Name	Description
DRUG	Linsitinib

Timeline

• Start date: 2014-03-01
• Primary completion: 2016-07-15
• Completion: 2016-07-15
• First posted: 2015-09-11
• Last updated: 2019-06-03
• Results posted: 2019-06-03

Locations

5 sites across 5 countries: France, Germany, Italy, Netherlands, United Kingdom