ISG/AIEOP EW-1: Randomised controlled trial for patients with non-metastatic Ewing sarcoma

ISRCTN	ISRCTN50580483
DOI	https://doi.org/10.1186/ISRCTN50580483
Clinical Trials Information System (CTIS)	2008-008361-35
Protocol serial number	N/A
Sponsor	Italian Sarcoma Group (Italy)
Funder	Italian Sarcoma Group (Italy)

Submission date: 29/03/2010
Registration date: 22/04/2010
Last edited: 18/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Ewing sarcoma is a rare type of bone cancer. It is treated with chemotherapy to kill the cancer cells. The aim of this study is to compare a prolonged chemotherapy treatment and a shorter dose-intense chemotherapy treatment for Ewing sarcoma.

Who can participate?
Patients aged under 41 with non-metastatic Ewing sarcoma (i.e., that has not spread)

What does the study involve?
Participants are randomly allocated to receive either the prolonged treatment or the shorter dose-intense treatment. The survival rate in both groups is assessed after four years.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Italian Sarcoma Group (Italy)

When is the study starting and how long is it expected to run for?
April 2009 to April 2016

Who is funding the study?
Italian Sarcoma Group (Italy)

Who is the main contact?
Dr Stefano Ferrari
stefano.ferrari@ior.it

Contact information

Dr Stefano Ferrari
Scientific

Via Pupilli 1
Bologna
40136
Italy

Email	stefano.ferrari@ior.it

Study information

Primary study design	Interventional
Study design	Randomised controlled phase III trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised controlled phase III trial of patients with non-metastatic Ewing sarcoma treated with either a prolonged treatment or a shorter dose-intense treatment and the effect on probability of survival
Study acronym	ISG/AIEOP EW-1
Study objectives	ISG/AIEOP EW-1 is a randomised phase III trial. The hypothesis tested is that the same probability of survival expected with a prolonged treatment can be achieved with a shorter and dose/intense treatment.
Ethics approval(s)	Ethics board of the Istituto Ortopedico Rizzoli, Bologna, Italy, 17/12/2008, EudraCT no.: 2008-008361-35
Health condition(s) or problem(s) studied	Non-metastatic Ewing sarcoma
Intervention	Standard arm and experimental arm are based on neoadjuvant chemotherapy. According to the histologic or radiographic response to primary chemotherapy patients will receive high-dose chemotherapy and peripheral stem cells transplantation. Standard arm: Alternating cycles with VAC (vincristine 1.5 mg/m^2 [top dose 2 mg], doxorubicin 80 mg/m^2, cyclophosphamide 1,200 mg/m^2), IVAc (ifosfamide 9 g/m^2, vincristine 1.5 mg/m^2 [top dose 2 mg], dactinomycin 1.5 mg/m^2 [top dose 2 mg]), IE (ifosfamide 9 g/m^2, etoposide 450 mg/m^2). In poor responder patients mobilising cycle with CE (cyclophosphamide 4,000 mg/m^2, etoposide 600 mg/m^2), high dose chemotherapy with busulfan (0.8 mg/kg x 4/day for 4 days) and melfalan (140 mg/m^2). Total duration of treatment: good responders 37 weeks, poor responders 25 weeks. Experimental arm: Alternating cycles with VAI (vincristine 1.5 mg/m^2 [top dose 2 mg], doxorubicin 80 mg/m^2, ifosfamide 9 g/m^2), IVAc (ifosfamide 9 g/m^2, vincristine 1.5 mg/m^2 [top dose 2 mg]), IE (ifosfamide 9 g/m^2, etoposide 450 mg/m^2). In poor responder patients mobilising cycle with CE (cyclophosfamide 4,000 mg/m^2, etoposide 600 mg/m^2), high dose chemotherapy with busulfan intravenous (I.V.) (0.8 mg/kg x 4/day for 4 days) and melfalan (140 mg/m^2). Total duration of treatment: good responders 25 weeks, poor responders 25 weeks. Total duration of follow-up for all arms: 5 years enrolment, 2 years follow-up.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Vincristine, dactinomycin, doxorubicin, cyclophosfamide, ifosfamide, etoposide, busulfan, melfalan
Primary outcome measure(s)	Overall survival, measured at four years
Key secondary outcome measure(s)	1. Event-free survival,measured at four years 2. Percent of patients with good response to primary chemotherapy 3. Received dose/intensity 4. Chemotherapy toxicity
Completion date	30/04/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	220
Key inclusion criteria	1. Patients with non-metastatic Ewing sarcoma 2. Aged less than 41 years, either sex 3. No previous treatment for the disease 4. Informed consent
Key exclusion criteria	1. Metastatic Ewing sarcoma 2. Medical contraindications to the protocol drugs
Date of first enrolment	11/04/2009
Date of final enrolment	30/04/2016

Locations

Countries of recruitment

Italy

Study participating centre

Via Pupilli 1

Bologna
40136
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

18/03/2016: Plain English summary added.