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)

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

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)