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Protocol for the Treatment of Metastatic Ewing Sarcoma

Phase 2
Completed
Conditions
Ewing's Sarcoma (ES)
Interventions
Drug: TEMIRI
Drug: CYC
Drug: ETO
Drug: BUMEL
Drug: VIN
Registration Number
NCT02727387
Lead Sponsor
Italian Sarcoma Group
Brief Summary

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

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
155
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELADM2cycles 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)
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELETO2cycles 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)
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELVIN2cycles 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)
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELTEMIRI2cycles 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)
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELCYC2cycles 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)
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELBUMEL2cycles 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)
TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMELIFO2cycles 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)
Primary Outcome Measures
NameTimeMethod
Event Free Survival (DFS)Expected average 1 year

Evaluation of the time in which the patient do not experience any progression, relapse of toxicity event when treated according to the protocol

Overall Survival (OS)Expected average 3 year

Evaluation of the OS in patients treated according to the protocol

Secondary Outcome Measures
NameTimeMethod
Evaluation of Quality of life using Pediatric Quality of Life Inventory (PedQL) -in child and adolescents(EORTC QLQ-C30) for children and adolescentsevery 3 weeks for the first 6 months and 3 monthly up to 1 year

Evaluation of patient's Quality of life: comparison of the Baseline and On treatrment quality of life score using PedQL

Safety - Incidence and grade of treatment-emergent Adverse Eventsevery 21 days up to 1 year

Incidence and grade of treatment-emergent Adverse Events

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 patientsevery 3 weeks for the first 6 months and 3 monthly up to 1 year

Evaluation of patient's Quality of life: comparison of the Baseline and On treatrment quality of life score using EORTC QLQ-C30

Trial Locations

Locations (13)

Azienda Ospedaliero-Universitaria Pisana

🇮🇹

Pisa, Italy

Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

🇮🇹

Torino, Italy

Centro di Riferimento Oncologico - Unit of Medical Oncology

🇮🇹

Aviano, Pordenone, Italy

Azienda ospedaliero universitaria consorziale policlinico - bari

🇮🇹

Bari, Italy

Servizio di Oncoematologi Pediatrica Ospedale microcitemico ASL 8

🇮🇹

Cagliari, Italy

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

🇮🇹

Bologna, Italy

A.O. Universitaria Meyer

🇮🇹

Firenze, Italy

I.R.C.C. - Unit of Medical Oncology

🇮🇹

Candiolo, Torino, Italy

Istituto Giannina Gaslini

🇮🇹

Genova, Italy

Fondazione IRCCS INT Milano

🇮🇹

Milano, Italy

Azienda Ospedaliera di Padova

🇮🇹

Padova, Italy

IRCCS materno infantile Burlo Garofolo

🇮🇹

Trieste, Italy

Ospedale Pediatrico Bambin Gesu'

🇮🇹

Roma, Italy

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