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

NCT02063022 | Completed Phase 3 DMC

• 1 other identifier: ISG/AIEOP EW-1
• Study Type: interventional
• Target: 278
• Locations: 1 country
• Sites: 14

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)

Conditions

Ewing's Sarcoma

Keywords

Non metastatic Ewing's Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Disease Free Survival (DFS)

  expected average 3 years

• Metastasis Free Survival

  expected average 2 years

• Overall Survival (OS)

  expected average 5 years

Study Arms (2)

Standard treatment (as per ISG SSG III protocol)

ACTIVE COMPARATOR

Standard treatment for non metastatic Ewing's Sarcoma (as defined by the ISG/SSG III protocol). It is based on a 6 drugs pre-local treatment (Vincristin, dactinomycin, cyclophosphamide,ifosfamide,etoposide and doxorubicin) followed by local treatment (surgery and/or radiotherapy)and by a maintenance treatment based on induction response

Drug: Standard treatment (as per protocol ISG SSG III)

Intensified treatment

EXPERIMENTAL

Dose intense treatment for non metastatic Ewing's Sarcoma It is based on a 3 drug pre-local treatment (Vincristin, ifosfamide and doxorubicin)followed by local treatment (surgery and/or radiotherapy)and by a maintenance treatment based on induction response

Drug: Intensified chemotherapy

Interventions

Standard treatment (as per protocol ISG SSG III) DRUG

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)

Also known as: Vincristine, Dactinomycin, Doxorubicin, Ifosfamide, Cyclophosphamide, Etoposide, Busulfan, Melphalan

Standard treatment (as per ISG SSG III protocol)

Intensified chemotherapy DRUG

* 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)

Also known as: Vincristine,, Doxorubicin, Ifosfamide, Cyclophosphamide, Etoposide, Busulfan, Melphalan

Intensified treatment

Eligibility Criteria

• Age: Up to 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Italian Sarcoma Group: lead

Study Sites (14)

Centro di Riferimento Oncologico - Unit of Medical Oncology

Aviano, Pordenone, 33081, Italy

Location

I.R.C.C. - Unit of Medical Oncology

Candiolo, Torino, 10060, Italy

Location

IRCCS materno infantile Burlo Garofolo

Trieste, T, 34137, Italy

Location

Azienda Ospedaliero Universitaria Consorziale Policlinico - Bari

Bari, 70124, Italy

Location

Istituto Ortopedico Rizzoli

Bologna, 40136, Italy

Location

A.O. Universitaria Meyer

Florence, 50139, Italy

Location

Istituto Giannina Gaslini

Genova, Italy

Location

FONDAZIONE IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Azienda Ospedaliera Universitaria "Federico Ii" .

Napoli, 80131, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I

Roma, 00144, Italy

Location

Ospedale Pediatrico Bambin Gesu'

Roma, Italy

Location

Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

Torino, 10126, Italy

Location

Related Publications (2)

• 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

  BACKGROUND

• Luksch R, Palmerini E, Milano GM, Paioli A, Asaftei S, Barretta F, Puma N, Cesari M, Tirtei E, Podda M, Pierobon M, Manzitti C, Ferraresi V, Tamburini A, Bertulli R, Di Pinto D, Mascarin M, Grignani G, Coccoli L, Rabusin M, De Leonardis F, Gambarotti M, Parafioriti A, Cammelli S, Vennarini S, Ferrari S, Donati DM, Bastoni S, Massimino M, Fagioli F, Ibrahim T. Intensified Induction Therapy for Newly Diagnosed, Localized Skeletal Ewing Sarcoma (ISG/AIEOP EW-1): A Randomized, Open-Label, Phase 3, Non-Inferiority Trial. Pediatr Blood Cancer. 2025 Apr;72(4):e31551. doi: 10.1002/pbc.31551. Epub 2025 Jan 20.

  PMID: 39833645 DERIVED

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Vincristine; Dactinomycin; Doxorubicin; Ifosfamide; Cyclophosphamide; Etoposide; Busulfan; Melphalan

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Heterocyclic Compounds, 3-Ring; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Roberto Luksch, MD

  Italian Sarcoma Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: February 14, 2014
• Study Start: January 22, 2009
• Primary Completion: April 14, 2022
• Study Completion: April 14, 2022
• Last Updated: September 19, 2022

Record last verified: 2022-09

Locations

IT (14)