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Trial record 7 of 33 for:    "Ewing Sarcoma" | "Vincristine"

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

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ClinicalTrials.gov Identifier: NCT02063022
Recruitment Status : Active, not recruiting
First Posted : February 14, 2014
Last Update Posted : June 10, 2019
Sponsor:
Information provided by (Responsible Party):
Italian Sarcoma Group

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)

Condition or disease Intervention/treatment Phase
Ewing's Sarcoma Drug: Standard treatment (as per protocol ISG SSG III) Drug: Intensified chemotherapy Phase 3

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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Study on Efficacy of Dose Intensification in Patients With Non-metastatic Ewing Sarcoma.
Actual Study Start Date : January 22, 2009
Estimated Primary Completion Date : December 20, 2021
Estimated Study Completion Date : December 20, 2021


Arm Intervention/treatment
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

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

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
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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)



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Ages Eligible for Study:   up to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02063022


Locations
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Italy
Centro di Riferimento Oncologico - Unit of Medical Oncology
Aviano, Pordenone, Italy, 33081
I.R.C.C. - Unit of Medical Oncology
Candiolo, Torino, Italy, 10060
Presidio Sanitario Gradenigo
Torino, TO, Italy, 10153
Istituto Ortopedico Rizzoli
Bologna, Italy, 40136
A.O. Universitaria Policlinico S. Orsola Malpighi di Bologna
Bologna, Italy, 40138
Servizio di Oncoematologi Pediatrica Ospedale microcitemico ASL 8
Cagliari, Italy, Rosamaria
A.O. Universitaria Meyer
Firenze, Italy, 50139
Istituto Giannina Gaslini
Genova, Italy
FONDAZIONE IRCCS Istituto Nazionale dei Tumori
Milano, Italy
Azienda Ospedaliera di Padova
Padova, Italy
Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I
Roma, Italy, 00144
Ospedale Pediatrico Bambin Gesu'
Roma, Italy
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
Torino, Italy, 10126
Sponsors and Collaborators
Italian Sarcoma Group
Investigators
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Principal Investigator: Stefano Ferrari, MD Italian Sarcoma Group

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

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Responsible Party: Italian Sarcoma Group
ClinicalTrials.gov Identifier: NCT02063022     History of Changes
Other Study ID Numbers: ISG/AIEOP EW-1
First Posted: February 14, 2014    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: June 2019
Keywords provided by Italian Sarcoma Group:
Non metastatic Ewing's Sarcoma
Additional relevant MeSH terms:
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Sarcoma, Ewing
Vincristine
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Dactinomycin
Cyclophosphamide
Melphalan
Busulfan
Ifosfamide
Isophosphamide mustard
Doxorubicin
Liposomal doxorubicin
Etoposide
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors