Clinical Trial: Eurosarc Trial of Linsitinib in Advanced Ewing Sarcoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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.


Sponsor: University of Oxford

Current Primary Outcome:

  • 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 ]
    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) ]
    Quantity and severity of


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical outcome (PFS, DSS, ORR) [ Time Frame: Duration of study (up to 18 months) ]

    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) ]
    Plasma concentrations of linsitinib will be measured and appropriate pharmacokinetic analysis will be performed


Original Secondary Outcome: Same as current

Information By: University of Oxford

Dates:
Date Received: August 6, 2014
Date Started: March 2014
Date Completion:
Last Updated: March 21, 2017
Last Verified: March 2017