Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma

Phase 3

Completed

• Conditions: Ewing's Sarcoma
• Interventions: Drug: Standard treatment (as per protocol ISG SSG III); Drug: Intensified chemotherapy

• Registration Number: NCT02063022
• Lead Sponsor: Italian Sarcoma Group

Brief Summary

Controlled, randomized phase III study, with the intent of optimizing the treatment of not metastatic Ewing Sarcoma. The patients will be randomized into 2 arms: standard treatment vs intensive treatment. Both arms will receive an induction treatment followed by surgery (wherever is possible) and/or radiotherapy. The maintenance treatment will be different on the basis of the response to the induction treatment (good or poor)

Detailed Description

Eligible patients with non metastatic Ewing's Sarcoma will be randomized into 2 different arms: standard treatment arm A (based on the ISG/SSG III protocol) or into the experimental arm B(chemotherapy with dose intensification and shorter length of treatment).

Both arm will receive an induction treatment with higher dose intensity of doxorubicin and ifosfamide in Arm B.

After the induction treatment all the patient will undergo to local treatment (surgery and/or radiotherapy)that will be followed by a maintenance therapy.

The maintenance therapy will be different for both arms and, within each arm, on the basis of the response (histologically evaluated) of the pre-local treatment therapy.

Maintenance for Arm A: Poor responders will undergo to stem cells apheresis and their reinfusion after treatment with high doses of Busulfan and Melphalan 25 weeks.

Good responders will receive a 6 drugs maintenance treatment for 37 weeks (as per standard ISG/SSG III protocol)

Maintenance for Arm B: Poor responders will undergo to stem cells apheresis and their reinfusion after an intensified treatment with high doses of Busulfan and Melphalan (25 weeks).

Good responders will receive a maintenance treatment for 25 weeks

The primary aim of the study is to assess the Event Free Survival (EFS) that is expected to be similar in both arms

The secondary objectives are:

To assess if the induction treatment in Arm B is able to increase the percentage of good responders compared to those who receive standard treatment.

To assess the toxicity and the Quality of Life related to the chemotherapy treatment

Study Timeline

• Study Start: 2009-01-22
• Study First Submitted: 2013-02-21
• Study First Submitted QC: 2014-02-13
• Study First Posted: 2014-02-14
• Primary Completion: 2022-04-14
• Study Completion: 2022-04-14
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-16
• Last Update Posted: 2022-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 278

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard treatment (as per ISG SSG III protocol)	Standard treatment (as per protocol ISG SSG III)	Standard treatment for non metastatic Ewing's Sarcoma (as defined by the ISG/SSG III protocol). It is based on a 6 drugs pre-local treatment (Vincristin, dactinomycin, cyclophosphamide,ifosfamide,etoposide and doxorubicin) followed by local treatment (surgery and/or radiotherapy)and by a maintenance treatment based on induction response
Intensified treatment	Intensified chemotherapy	Dose intense treatment for non metastatic Ewing's Sarcoma It is based on a 3 drug pre-local treatment (Vincristin, ifosfamide and doxorubicin)followed by local treatment (surgery and/or radiotherapy)and by a maintenance treatment based on induction response

Primary Outcome Measures

Name	Time	Method
Event Free Survival (EFS)	5 years	The EFS (event defined as Progressive Disease , onset of local relapse and/or metastasis, death due to chemotherapy toxicity or for other causes) will be calculated from the first treatment day up to the event onset or to last follow-up

Secondary Outcome Measures

Name	Time	Method
Disease Free Survival (DFS)	expected average 3 years	The DFS will be calculated from the day that the patient will be free from disease (surgery date and/or radiotherapy completion) up to the date of progression disease or last follow-up
Overall Survival (OS)	expected average 5 years	The OS will be evaluated for the start treatment day to the day of death (for any causes)
Metastasis Free Survival	expected average 2 years	The Metastasis free Survival will be evaluated from the time of disease free (surgery performed and/or radiotherapy completed) to the onset of distance metastasis or last follow-up

Trial Locations

Locations (14)

I.R.C.C. - Unit of Medical Oncology; 🇮🇹 Candiolo, Torino, Italy

Azienda Ospedaliera Universitaria "Federico Ii" .; 🇮🇹 Napoli, Italy

Centro di Riferimento Oncologico - Unit of Medical Oncology; 🇮🇹 Aviano, Pordenone, Italy

IRCCS materno infantile Burlo Garofolo; 🇮🇹 Trieste, T, Italy

Azienda Ospedaliero Universitaria Consorziale Policlinico - Bari; 🇮🇹 Bari, Italy

Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy

A.O. Universitaria Meyer; 🇮🇹 Firenze, Italy

Istituto Giannina Gaslini; 🇮🇹 Genova, Italy

FONDAZIONE IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Azienda Ospedaliera di Padova; 🇮🇹 Padova, Italy

Azienda Ospedaliero Universitaria Pisana; 🇮🇹 Pisa, Italy

Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I; 🇮🇹 Roma, Italy

Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology; 🇮🇹 Torino, Italy

Ospedale Pediatrico Bambin Gesu'; 🇮🇹 Roma, Italy