Clinical trial NCT02063022: Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma
Official title: Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ewing's Sarcoma
Keywords: Non metastatic Ewing's Sarcoma
Lead sponsor: Italian Sarcoma Group
Sponsor class: NETWORK
First posted: 2014-02-14
Enrollment: 278
Sex: ALL
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Detailed 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

Eligibility criteria: 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)

Primary outcomes:
measure: Event Free Survival (EFS)
timeFrame: 5 years
Secondary outcomes:
measure: Disease Free Survival (DFS)
timeFrame: expected average 3 years
measure: Metastasis Free Survival
timeFrame: expected average 2 years
measure: Overall Survival (OS)
timeFrame: expected average 5 years
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Unit of Medical Oncology
state: Pordenone
city: Candiolo
country: Italy
facility: I.R.C.C. - Unit of Medical Oncology
state: Torino
city: Trieste
country: Italy
facility: IRCCS materno infantile Burlo Garofolo
state: T
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico - Bari
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Firenze
country: Italy
facility: A.O. Universitaria Meyer
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Milano
country: Italy
facility: FONDAZIONE IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico Ii" .
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambin Gesu'
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
Study officials:
affiliation: Italian Sarcoma Group
name: Roberto Luksch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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