Ewing's SarcomaPhase 3EW-1NCT02063022
Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma
A Phase 3 study testing Standard treatment (as per protocol ISG SSG III) and Intensified chemotherapy in people with Ewing's Sarcoma, run by Italian Sarcoma Group at 14 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages Up to 40 years
- Conditions the study is for
- Ewing's Sarcoma
- What is being tested?
- Standard treatment (as per protocol ISG SSG III) and Intensified chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 278 participants
- Where
- 14 sitesItaly
- Study dates
- 22 Jan 2009to 14 Apr 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Italy14 sites
Centro di Riferimento Oncologico - Unit of Medical Oncology
Aviano, Pordenone, 33081
Azienda Ospedaliero Universitaria Consorziale Policlinico - Bari
Bari, 70124
Istituto Ortopedico Rizzoli
Bologna, 40136
I.R.C.C. - Unit of Medical Oncology
Candiolo, Torino, 10060
A.O. Universitaria Meyer
Florence, 50139
Istituto Giannina Gaslini
Genova
FONDAZIONE IRCCS Istituto Nazionale dei Tumori
Milan
Azienda Ospedaliera Universitaria "Federico Ii" .
Naples, 80131
Azienda Ospedaliera di Padova
Padova
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I
Roma, 00144
Ospedale Pediatrico Bambin Gesu'
Roma
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
Torino, 10126
IRCCS materno infantile Burlo Garofolo
Trieste, T, 34137
About this study
Official title: Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.
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)
Read the 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
- Conditions
- Ewing's Sarcoma
- Being tested
- Standard treatment (as per protocol ISG SSG III), Intensified chemotherapy
- Keywords
- Non metastatic Ewing's Sarcoma
- Medical subject headings
- Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard treatment (as per protocol ISG SSG III)Drug
Also called Vincristine, Dactinomycin, Doxorubicin, Ifosfamide
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 chemotherapyDrug
Also called Vincristine,, Doxorubicin, Ifosfamide, Cyclophosphamide
- 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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Intensified chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Secondary outcomes (3)
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
Measured: expected average 3 years
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
Measured: expected average 2 years
Overall Survival (OS)
The OS will be evaluated for the start treatment day to the day of death (for any causes)
Measured: expected average 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2014 (estimated)
- Study start22 Jan 2009
- Primary completion14 Apr 2022
- Study completion14 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 278 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italian Sarcoma Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Roberto Luksch, MD, Principal investigator, Italian Sarcoma Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02063022
- Sponsor's protocol ID
- ISG/AIEOP EW-1
- Acronym
- EW-1
- Status last verified
- Sep 2022
- First submitted
- 21 Feb 2013
- Last updated
- 19 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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
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.
PubMed 39833645
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.
- ClinicalTrials.gov ID
- NCT02063022
- Acronym / sponsor ID
- EW-1 / ISG/AIEOP EW-1
- Conditions
- Ewing's Sarcoma
- Keywords
- Non metastatic Ewing's Sarcoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 278 participants (actual)
- Lead sponsor
- Italian Sarcoma GroupResearch network
- Study start
- 22 Jan 2009 (actual)
- Primary completion
- 14 Apr 2022 (actual)
- Study completion
- 14 Apr 2022 (actual)
- First posted
- 14 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard treatment (as per ISG SSG III protocol) | Active comparator | Drug: Standard treatment (as per protocol ISG SSG III)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 |
| Intensified treatment | Experimental | Drug: Intensified chemotherapyDose 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 |
Who may qualify
- Ages
- Up to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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%
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard treatment (as per protocol ISG SSG III)Also: Vincristine, Dactinomycin, Doxorubicin, IfosfamideInduction 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) | Drug | Standard treatment (as per ISG SSG III protocol) |
| Intensified chemotherapyAlso: Vincristine,, Doxorubicin, Ifosfamide, Cyclophosphamide* 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) | Drug | Intensified treatment |
Primary outcome
Event Free Survival (EFS)
Time frame: 5 years
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
3 secondary outcomes
Disease Free Survival (DFS)
Time frame: expected average 3 years
Metastasis Free Survival
Time frame: expected average 2 years
Overall Survival (OS)
Time frame: expected average 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2022.
- BackgroundS. 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
- Derived from this study: PubMed 39833645Luksch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberto Luksch, MD principal investigator
Italian Sarcoma Group
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Standard treatment (as per protocol ISG SSG III) and Intensified chemotherapy in people with Ewing's Sarcoma, run by Italian Sarcoma Group at 14 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival (EFS) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02063022, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2022.