EW-2: Protocol for the Treatment of Metastatic Ewing Sarcoma
Study Details
Study Description
Brief Summary
Study for the treatment of metastatic Ewing sarcoma with high doses chemotherapy, radiotherapy and maintenance therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TEMIRI+VIN+ADM+IFO+ CYC+ETO+BUMEL 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
Window therapy frontline for VHR patients
Other Names:
Drug: ADM
Drug used in the Induction phase in association with Vincristine, Ifosfamide, cyclophosphamide and Etoposide
Other Names:
Drug: IFO
Drug used in the Induction phase in association with Vincristine, Adriamycin, cyclophosphamide and Etoposide
Other Names:
Drug: CYC
Drug used in the Induction phase in association with Vincristine, Ifosfamide, Adriamycin and Etoposide
Other Names:
Drug: ETO
Drug used in the Induction phase in association with Vincristine, Ifosfamide, cyclophosphamide and Adriamycin
Other Names:
Drug: BUMEL
Consolidation phase
Other Names:
Drug: VIN
Drug used in the Induction phase in association with cyclophosphamide , Ifosfamide, Adriamycin and Etoposide
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Expected average 3 year]
Evaluation of the OS in patients treated according to the protocol
- 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
Secondary Outcome Measures
- Safety - Incidence and grade of treatment-emergent Adverse Events [every 21 days up to 1 year]
Incidence and grade of treatment-emergent Adverse Events
- Evaluation of Quality of life using Pediatric Quality of Life Inventory (PedQL) -in child and adolescents(EORTC QLQ-C30) for children and adolescents [every 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
- 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 [every 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centro di Riferimento Oncologico - Unit of Medical Oncology | Aviano | Pordenone | Italy | 33081 |
| 2 | I.R.C.C. - Unit of Medical Oncology | Candiolo | Torino | Italy | 10060 |
| 3 | Azienda ospedaliero universitaria consorziale policlinico - bari | Bari | Italy | 70124 | |
| 4 | Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors | Bologna | Italy | 40136 | |
| 5 | Servizio di Oncoematologi Pediatrica Ospedale microcitemico ASL 8 | Cagliari | Italy | Rosamaria | |
| 6 | A.O. Universitaria Meyer | Firenze | Italy | 50139 | |
| 7 | Istituto Giannina Gaslini | Genova | Italy | ||
| 8 | Fondazione IRCCS INT Milano | Milano | Italy | ||
| 9 | Azienda Ospedaliera di Padova | Padova | Italy | 35128 | |
| 10 | Azienda Ospedaliero-Universitaria Pisana | Pisa | Italy | 56126 | |
| 11 | Ospedale Pediatrico Bambin Gesu' | Roma | Italy | ||
| 12 | Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology | Torino | Italy | 10126 | |
| 13 | IRCCS materno infantile Burlo Garofolo | Trieste | Italy | 34137 |
Sponsors and Collaborators
- Italian Sarcoma Group
Investigators
- Principal Investigator: Roberto Luksch, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study Documents (Full-Text)
None provided.More Information
Publications
- Gardner SL, Carreras J, Boudreau C, Camitta BM, Adams RH, Chen AR, Davies SM, Edwards JR, Grovas AC, Hale GA, Lazarus HM, Arora M, Stiff PJ, Eapen M. Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma. Bone Marrow Transplant. 2008 May;41(10):867-72. doi: 10.1038/bmt.2008.2. Epub 2008 Feb 4.
- Paulussen M, Ahrens S, Burdach S, Craft A, Dockhorn-Dworniczak B, Dunst J, Fröhlich B, Winkelmann W, Zoubek A, Jürgens H. Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. European Intergroup Cooperative Ewing Sarcoma Studies. Ann Oncol. 1998 Mar;9(3):275-81.
- Picci P, Böhling T, Bacci G, Ferrari S, Sangiorgi L, Mercuri M, Ruggieri P, Manfrini M, Ferraro A, Casadei R, Benassi MS, Mancini AF, Rosito P, Cazzola A, Barbieri E, Tienghi A, Brach del Prever A, Comandone A, Bacchini P, Bertoni F. Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities. J Clin Oncol. 1997 Apr;15(4):1553-9.
- ISG/AIEOP EW-2