Protocol for the Treatment of Metastatic Ewing Sarcoma

Study Overview
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Brief Summary
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Study for the treatment of metastatic Ewing sarcoma with high doses chemotherapy, radiotherapy and maintenance therapy.

Detailed Description
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Study for the treatment of Ewing metastatic sarcoma with and induction phase with Vincristine (VIN), Adriamycin (ADM), Ciclofosfamide(CYC), Ifosfamide(IFO), Etoposide(ETO) and radiotherapy (RT)followed by a consolidation phase with Busulfan and Melfalan (BUMEL) and Peripheral Blood Stem Cells Transplantation (PBSCT) and a subsequent maintenance phase with Ciclofosfamide and Celecoxib for High Risk (HR) patients. Very High Risk (VHR) patients will receive a prior frontline therapy with Temozolomide and Irinotecan (TEMIRI), while patient with lung metastasis only will undergo to total lung irradiation after PBSCT

Official Title
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Study With High Doses of Chemotherapy, Radiotherapy and Consolidation Therapy With Ciclofosfamide and Anticyclooxygenase 2, for the Metastatic Ewing Sarcoma

Conditions
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Ewing's Sarcoma (ES)

Intervention / Treatment
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* Drug: TEMIRI
* Drug: ADM
* Drug: IFO
* Drug: CYC
* Drug: ETO
* Drug: BUMEL
* Drug: VIN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven Ewing's sarcoma Age ≤ 40 years No previous treatment Multiple skeletal metastasis or bone marrow infiltration , with/without lung/pleural metastasis Signed Informed Consent Exclusion Criteria: Localized Ewing's sarcoma Any contraindications to the study treatment Female patients who not accept to use an effective birth control method. Pregnant or breast-feeding patients

Ages Eligible for Study
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Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMEL<br>2cycles of Temozolomide(500 mg/m2)+Irinotecan(250 mg/m2) and 2cycles of Vincristine(1.4mg/m2)+ Adriamycin(90mg/m2)+Ifosfamide (9gr/m2) alternes with 2 cycles of Ciclofosfamide(4g/m2)+Etoposide (600mg/m2) followed by radiotherapy (42-54 Gy) and 2cycles of Ifosfamide (9gr/m2) + Etoposide(300mg/m2) alternes with to 2cycles of Vincristine (1.4mg/m2)+ Adriamycin (80mg/m2)+ Ciclofosfamide(1.2g/m2) and Busulfan(0.8-1.2 mg/Kg)+Melfalan(140 mg/m2)+PBSCT and 6 months with Celecoxib (500mg/m2/die for<14 years old ,800 mg/die for>14 years old) Ciclofosfamide (oral therapy 35mg/m2/die for<14 years old, 50 mg/m2 for>14 years old) | Drug: TEMIRI<br>* Window therapy frontline for VHR patients<br>* Other names: Temozolomide + Irinotecan;Drug: ADM<br>* Drug used in the Induction phase in association with Vincristine, Ifosfamide, cyclophosphamide and Etoposide<br>* Other names: Adriamycin;Drug: IFO<br>* Drug used in the Induction phase in association with Vincristine, Adriamycin, cyclophosphamide and Etoposide<br>* Other names: Ifosfamide;Drug: CYC<br>* Drug used in the Induction phase in association with Vincristine, Ifosfamide, Adriamycin and Etoposide<br>* Other names: Cyclophosphamide;Drug: ETO<br>* Drug used in the Induction phase in association with Vincristine, Ifosfamide, cyclophosphamide and Adriamycin<br>* Other names: Etoposide;Drug: BUMEL<br>* Consolidation phase<br>* Other names: busulfan + melphalan;Drug: VIN<br>* Drug used in the Induction phase in association with cyclophosphamide , Ifosfamide, Adriamycin and Etoposide<br>* Other names: Vincristine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Evaluation of the OS in patients treated according to the protocol | Expected average 3 year | 
| Event Free Survival (DFS) | Evaluation of the time in which the patient do not experience any progression, relapse of toxicity event when treated according to the protocol | Expected average 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Incidence and grade of treatment-emergent Adverse Events | Incidence and grade of treatment-emergent Adverse Events | every 21 days up to 1 year | 
| Evaluation of Quality of life using Pediatric Quality of Life Inventory (PedQL) -in child and adolescents(EORTC QLQ-C30) for children and adolescents | Evaluation of patient's Quality of life: comparison of the Baseline and On treatrment quality of life score using PedQL | every 3 weeks for the first 6 months and 3 monthly up to 1 year | 
| Evaluation of Quality of life using European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients (EORTC QLQ-C30) for adult patients | Evaluation of patient's Quality of life: comparison of the Baseline and On treatrment quality of life score using EORTC QLQ-C30 | every 3 weeks for the first 6 months and 3 monthly up to 1 year |