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

Ewing's Sarcoma Clinical Trial

— EW-1  

Official title:

Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02063022
• Other study ID #: ISG/AIEOP EW-1
• Status: Completed
• Phase: Phase 3
• Start date: January 22, 2009
• Est. completion date: April 14, 2022

Study information

• Verified date: September 2022
• Source: Italian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: April 14, 2022
• Est. primary completion date: April 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 40 Years

Eligibility

Inclusion Criteria

• Ewing Sarcoma or PNET diagnosis centrally confirmed
• Age = 40 years
• Absence of evident metastasis or lung met < 0.5 cm Presence of skip metastasis in the bone compartment of the primary tumor is to be considered as local disease and not metastatic.
• Adeguate bone marrow, hepatic and renal function
• Left Ventricular Ejection Fraction > 50%
• No primary Ewing Sarcoma treatments (both chemotherapy and/or radiotherapy)
• Voluntarily signed an informed consent form
• Radiological and histological documentation available for central review. Exclusion Criteria
• Presence of lung or extra-pulmonary lesions
• Bone Marrow involvement
• In case of chest disease: presence of plural effusion
• Elapsed time between histological diagnosis and chemotherapy start, more than 4 weeks
• Any medical contraindication to the use of the study drugs
• Any psychological or social conditions that can compromise the protocol compliance and/or follow-up
• Previous malignancies (excluded in situ cervix carcinoma)

Related Conditions & MeSH terms

• Ewing's Sarcoma
• Sarcoma
• Sarcoma, Ewing

Intervention

Drug:
• Standard treatment (as per protocol ISG SSG III)
Induction treatment with: 4 cycle of Vincristine (9mg/,2), Dactinomycin (6mg/m2), Doxorubicin (160mg/m2), Cyclophosphamide (2.4g/m2), Ifosfamide (18g/M2) and Etoposide (450mg/m2) given every 3 weeks Maintenance treatment for poor responder (25 weeks): Vincristine (12mg/m2), Dactinomycin (1.5mg/m2), Doxorubicin (320mg/m2), Ifosfamide (27g/m2), Cyclophosphamide (8.8g/m2), Etoposide (1.5g/m2) and peripheral Cells Steam Transplant after Busulfan and Melphalan treatment Maintenance treatment (37 week) for good responder: Vincristine (18mg/m2), Dactinomycin (6mg/m2), Doxorubicin (400mg/m2), Ifosfamide (72g/m2), Cyclosphosphamide(6g/m2), Etoposide (1.8 g/m2)
• Intensified chemotherapy
Induction treatment with: 4 cycle of Vincristine (10.5 mg/m2), Doxorubicin (320 mg/m2) and Ifosfamide (36 mg/m2) given every 3 weeks Maintenance treatment for poor responder (25 weeks): Vincristine (12mg/m2), Doxorubicin (400mg/m2), Ifosfamide (63g/m2), Cyclophosphamide (4g/m2), Etoposide (1.5g/m2) and Cells Steam Transplant after Busulfan and Melphalan treatment Maintenance treatment (25 week) for good responder: Vincristine (12mg/m2), Doxorubicin (400mg/m2), Ifosfamide (72g/m2), Etoposide (1.8g/m2)

Locations

Country	Name	City	State
Italy	Centro di Riferimento Oncologico - Unit of Medical Oncology	Aviano	Pordenone
Italy	Azienda Ospedaliero Universitaria Consorziale Policlinico - Bari	Bari
Italy	Istituto Ortopedico Rizzoli	Bologna
Italy	I.R.C.C. - Unit of Medical Oncology	Candiolo	Torino
Italy	A.O. Universitaria Meyer	Firenze
Italy	Istituto Giannina Gaslini	Genova
Italy	FONDAZIONE IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Azienda Ospedaliera Universitaria "Federico Ii" .	Napoli
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 Pediatrico Bambin Gesu'	Roma
Italy	Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology	Torino
Italy	IRCCS materno infantile Burlo Garofolo	Trieste	T

Sponsors (1)

Lead Sponsor	Collaborator
Italian Sarcoma Group

Country where clinical trial is conducted

Italy, 

References & Publications (1)

S. Ferrari, T. Alvegard, R. Luksch, A. Tienghi, K. S. Hall, G. Bernini, A. Brach del Prever, P. Picci, G. Bacci, S. Smeland Non-metastatic Ewing's family tumors: High-dose chemotherapy with stem cell rescue in poor responder patients. Preliminary results of the Italian/Scandinavian ISG/SSG III protocol. J Clini Oncol, 2007 ASCO Annual Meeting Proceedings Vol 25 (June 20 Suppl), 2007: 10014

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival (EFS)	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	5 years
Secondary	Disease Free Survival (DFS)	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	expected average 3 years
Secondary	Metastasis Free Survival	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	expected average 2 years
Secondary	Overall Survival (OS)	The OS will be evaluated for the start treatment day to the day of death (for any causes)	expected average 5 years