Conditions: Relapsed Ewing Sarcoma Refractory Ewing Sarcoma
Keywords: Linsitinib anti-IGF-1R/IR Ewing Sarcoma dual IGF-1R/IR inhibition Relapsed Ewing Sarcoma Refractory Ewing Sarcoma Metastatic Ewing Sarcoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 16
Healthy volunteers: no

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 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.

Arms:
arm 1: Linsitinib is to be taken orally once a day on days 1-3, 8-10 and 15-17 on a 21 day cycle. The starting dose is 600 mg

Interventions: intervention 1: Linsitinib
Intervention descriptions: intervention 1: None

Protocol document: