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Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma (EW-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02063022
Recruitment Status : Active, not recruiting
First Posted : February 14, 2014
Last Update Posted : February 17, 2020
Sponsor:
Information provided by (Responsible Party):
Italian Sarcoma Group

Tracking Information
First Submitted Date  ICMJE February 21, 2013
First Posted Date  ICMJE February 14, 2014
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE January 22, 2009
Estimated Primary Completion Date December 20, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2014)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2014)
  • Disease Free Survival (DFS) [ Time Frame: expected average 3 years ]
    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
  • Metastasis Free Survival [ Time Frame: expected average 2 years ]
    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
  • Overall Survival (OS) [ Time Frame: expected average 5 years ]
    The OS will be evaluated for the start treatment day to the day of death (for any causes)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma
Official Title  ICMJE Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ewing's Sarcoma
Intervention  ICMJE
  • Drug: Standard treatment (as per protocol ISG SSG III)
    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)
    Other Names:
    • Vincristine
    • Dactinomycin
    • Doxorubicin
    • Ifosfamide
    • Cyclophosphamide
    • Etoposide
    • Busulfan
    • Melphalan
  • Drug: Intensified chemotherapy
    • 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)
    Other Names:
    • Vincristine,
    • Doxorubicin
    • Ifosfamide
    • Cyclophosphamide
    • Etoposide
    • Busulfan
    • Melphalan
Study Arms  ICMJE
  • Active Comparator: Standard treatment (as per ISG SSG III protocol)

    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

    Intervention: Drug: Standard treatment (as per protocol ISG SSG III)
  • Experimental: Intensified treatment
    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
    Intervention: Drug: Intensified chemotherapy
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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 9, 2019)
242
Original Estimated Enrollment  ICMJE
 (submitted: February 13, 2014)
220
Estimated Study Completion Date  ICMJE December 20, 2021
Estimated Primary Completion Date December 20, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02063022
Other Study ID Numbers  ICMJE ISG/AIEOP EW-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Italian Sarcoma Group
Study Sponsor  ICMJE Italian Sarcoma Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Roberto Luksch, MD Italian Sarcoma Group
PRS Account Italian Sarcoma Group
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP