Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years (CombinaiR3)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03011528
Recruitment Status : Recruiting
First Posted : January 5, 2017
Last Update Posted : October 15, 2018
Sponsor:
Collaborator:
UNICANCER
Information provided by (Responsible Party):
Institut Curie

Brief Summary:

Ewing's sarcoma and related tumours (ESFT) are rare tumours, with a peak incidence in the second decade of life. They start most often from bone, and are characterized by a specific translocation involving the so-called EWS gene. In one patient out of three, the staging procedures detect metastatic tumours at the diagnosis, most commonly in lungs, bones, and bone marrow.

ESFT treatment strategy is multidisciplinary, combining primary chemotherapy, a local treatment, and consolidation chemotherapy.

The primary metastatic dissemination is the most important prognostic factor, as the survival rate is around 70-75% for localized tumours, in contrast with less than 50% for patients with primary metastatic disease.

Among primary metastatic patients, bone involvement and / or bone marrow strike markedly the prognosis of these patients. While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50%, whereas it is only from 0 to 25% in patients with bone marrow involvement.

In 1999, the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours. For the patients with primary extrapulmonary metastatic Ewing tumours (R3 patients), the protocol proposed a heavy induction chemotherapy, in order to propose a consolidation with high dose chemotherapy to a higher rate of patients. The high-dose Busulfan Melphalan chemotherapy (BuMel) was based on Busulfan (600 mg/m²) and Melphalan (140 mg/m²), with autologous peripheral blood stem cell (PBSC) support.

Of note, for the full population of patients with metastatic disease, the 3-year EFS rate was 27% (SD 3%), and the OS rate was 34% (SD 4%), with a median follow-up of 3.9 years after diagnosis, and a median survival time of 1.6 years.


Condition or disease Intervention/treatment Phase
Ewing Sarcoma Family of Tumors Drug: VDC-IE x2 Drug: VDC-IE Drug: TEMIRI Drug: Consolidation BuMel Drug: Maintenance Procedure: Local treatment by surgery Radiation: Local treatment by radiotherapy Phase 2

Detailed Description:

Ewing's sarcoma and related tumours (ESFT) are rare tumours, with a peak incidence in the second decade of life. They start most often from bone, and are characterized by a specific translocation involving the so-called EWS gene. The gene rearrangement results in the production of a transcription factor, in the majority EWS-FLI1 transcription.

In one patient out of three, the staging procedures detect metastatic tumours at the diagnosis; metastases involve most commonly lungs, bones, and bone marrow.

Therefore, in addition to local imaging, the initial extension assessment of any Ewing tumour includes at least a chest CT scan, and a bone marrow extensive evaluation, comprising bone marrow punctures into several different sectors, bone marrow biopsies, and a bone imaging evaluation. The FDG-PET scan is more sensible than bone scan and conventional imaging as MRI in detection of bone metastases. It is more and more widely used in the bone metastasis search in Ewing tumours and seems useful to complement the search of extra-osseous metastases (outside the lungs), including that of bone marrow metastases. The full-body MRI is still under evaluation for the disease extension evaluation.

ESFT treatment strategy is multidisciplinary, combining primary chemotherapy, a local treatment, and consolidation chemotherapy. The local treatment may combine surgery and / or radiotherapy, according to the tumour site and size, and to the tumour response. ESFT chemotherapy is based on alkylating agents (ifosfamide and / or cyclophosphamide), etoposide, anthracyclines, vincristine, and actinomycin.

The primary metastatic dissemination is the most important prognostic factor, as the survival rate is around 70-75% for localized tumours, in contrast with less than 50% for patients with primary metastatic disease. Among primary metastatic patients, bone involvement and / or bone marrow strike markedly the prognosis of these patients. While the long-term survival of patients with isolated pleural pulmonary metastases is approximately 50%, whereas it is only from 0 to 25% in patients with bone marrow involvement.

In 1999, the Intergroup EURO EWING built a new study protocol for patients with Ewing tumours, localized or metastatic and below 50 years of age. For the patients with primary extrapulmonary metastatic Ewing tumours (R3 patients), the protocol proposed a heavy induction chemotherapy, in order to propose a consolidation with high dose chemotherapy to a higher rate of patients. The high-dose BuMel chemotherapy was based on Busulfan (600 mg/m²) and Melphalan (140 mg/m²), with autologous peripheral blood stem cell (PBSC) support.

The study enrolled 281 patients with primary dissemination and skeletal metastases, with or without bone marrow involvement and with or without additional pulmonary metastases or metastases to other sites. In contrast to the distribution in the entire group of patients with Ewing tumours, the primary site in this subgroup was extremity in only 31% patients, pelvis/abdomen in 45%, and axial/other in 24% patients. The overall survival at 3 years was 28% (SD 4%) in the group with primary tumour in the abdomen or pelvis, versus 39% (SD 6%) for each of the two other groups. Of note, for the full population of patients with metastatic disease, the 3-year EFS rate was 27% (SD 3%), and the OS rate was 34% (SD 4%), with a median follow-up of 3.9 years after diagnosis, and a median survival time of 1.6 years.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CombinaiR3 - First-line Treatment of Ewing Tumours With Primary Extrapulmonary Dissemination in Patients From 2 to 50 Years
Study Start Date : December 2016
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
VDC - IE x2 & Surgery

Patients in Arm A receive

  • VDC-IE x2: Intensified induction phase:

    • 4 cycles of VDC (Vincristine Doxorubicine Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "good response" after the 4th treatment, followed by:
    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association
  • Consolidation BuMel High dose chemotherapy (Busulfan Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Local treatment by surgery of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision. Radiotherapy can be added
  • Maintenance phase

    • 1st year : VCC (Vincristine Cyclophosphamide Celecoxib) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: VDC-IE x2

Week 1, 5, 9 and week 13:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, 7, 11 and week 15:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Name: Intensified Induction VDC-IE x2

Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Name: High dose Consolidation chemotherapy

Drug: Maintenance
  • 1st year : VCC

    • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
    • Cyclophosphamide, PO, 25mg/m² continuously
    • Celecoxib, PO, according to the weight, twice a day, continuously, (except during radiation therapy)
  • < 20kg: 100 mg bid
  • 20-50kg: 200 mg bid
  • > 50kg: 400 mg bid
Other Name: 2 years maintenance

Procedure: Local treatment by surgery
Surgical excision of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy. Radiotherapy can be added
Other Name: Surgery of primary tumour/metastatic sites

Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Name: Radiotherapy of primary tumour/metastatic sites

VDC - IE & TEMIRI & Surgery

Patients in Arm B receive

  • VDC-IE & TEMIRI: Intensified induction phase:

    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "poor response" after the 4th treatment, followed by:
    • 4 cycles of TEMIRI (Temozolomide-Irinotecan) association
  • Local treatment by surgery of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision. Radiotherapy can be added
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Maintenance phase

    • 1st year : VCC (Vincristine Cyclophosphamide Celecoxib) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: VDC-IE

Week 1 and week 5:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, and week 7:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Name: Intensified Induction VDC-IE

Drug: TEMIRI

Week 9, 12, 15 and week 18:

  • Temozolomide, PO, D1 to D5, 150mg/m²/d
  • Irinotecan, IV, D1 to D5, 50mg/m²/d
Other Name: Intensified Induction TEMIRI

Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Name: High dose Consolidation chemotherapy

Drug: Maintenance
  • 1st year : VCC

    • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
    • Cyclophosphamide, PO, 25mg/m² continuously
    • Celecoxib, PO, according to the weight, twice a day, continuously, (except during radiation therapy)
  • < 20kg: 100 mg bid
  • 20-50kg: 200 mg bid
  • > 50kg: 400 mg bid
Other Name: 2 years maintenance

Procedure: Local treatment by surgery
Surgical excision of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy. Radiotherapy can be added
Other Name: Surgery of primary tumour/metastatic sites

Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Name: Radiotherapy of primary tumour/metastatic sites

VDC - IE x2 & Radiotherapy

Patients in Arm C receive

  • VDC-IE x2: Intensified induction phase:

    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "good response" after the 4th treatment, followed by:
    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Local treatment by radiotherapy of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision.
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Maintenance phase

    • 1st year : VCC (Vincristine Cyclophosphamide Celecoxib) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: VDC-IE x2

Week 1, 5, 9 and week 13:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, 7, 11 and week 15:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Name: Intensified Induction VDC-IE x2

Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Name: High dose Consolidation chemotherapy

Drug: Maintenance
  • 1st year : VCC

    • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
    • Cyclophosphamide, PO, 25mg/m² continuously
    • Celecoxib, PO, according to the weight, twice a day, continuously, (except during radiation therapy)
  • < 20kg: 100 mg bid
  • 20-50kg: 200 mg bid
  • > 50kg: 400 mg bid
Other Name: 2 years maintenance

Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Name: Radiotherapy of primary tumour/metastatic sites

VDC - IE & TEMIRI & Radiotherapy

Patients in Arm D receive

  • VDC-IE & TEMIRI: Intensified induction phase:

    • 4 cycles of VDC (Vincristine-Doxorubicine-Cyclophosphamide) association alternative with 4 cycles of IE (Ifosfamide-Etoposide) association if "poor response" after the 4th treatment, followed by:
    • 4 cycles of TEMIRI (Temozolomide-Irinotecan) association
  • Local treatment by radiotherapy of primary tumour/metastatic sites (outside pulmonary sites): indicated before of after consolidation phase (BuMel) among multidisciplinary decision.
  • Consolidation BuMel High dose chemotherapy (Busulfan-Melphalan) followed by Peripheral Blood Stem Cell Infusion
  • Maintenance phase

    • 1st year : VCC (Vincristine Cyclophosphamide Celecoxib) association
    • 2nd year : Cyclophosphamide po 25 mg/m²
Drug: VDC-IE

Week 1 and week 5:

  • Vincristine, IV, D1, 1.5mg/m²
  • Doxorubicine, IV, D1-D2, 37.5mg/m²
  • Cyclophosphamide, IV, D1, 1.2g/m²

Week 3, and week 7:

  • Ifosfamide, IV, D15 to D19, 1.8g/m²/d
  • Etoposide, IV, D15 to D19, 100mg/m²/d
Other Name: Intensified Induction VDC-IE

Drug: TEMIRI

Week 9, 12, 15 and week 18:

  • Temozolomide, PO, D1 to D5, 150mg/m²/d
  • Irinotecan, IV, D1 to D5, 50mg/m²/d
Other Name: Intensified Induction TEMIRI

Drug: Consolidation BuMel

After induction phase and local treatment (surgery and/or radiotherapy) and before PBSC:

  • Busulfan, IV, D-5 to D-2, dosa according to the weight
  • Melphalan, IV, D-1, 140 mg/m²

Peripheral Blood Stem Cell infusion:

- PBSC infusion, D0, at least 3.10^6 CD34/kg

Other Name: High dose Consolidation chemotherapy

Drug: Maintenance
  • 1st year : VCC

    • Vinblastine, IV, 3mg/m², once a week (except during radiotherapy: 1mg/m², 3 times a week)
    • Cyclophosphamide, PO, 25mg/m² continuously
    • Celecoxib, PO, according to the weight, twice a day, continuously, (except during radiation therapy)
  • < 20kg: 100 mg bid
  • 20-50kg: 200 mg bid
  • > 50kg: 400 mg bid
Other Name: 2 years maintenance

Radiation: Local treatment by radiotherapy
Radiotherapy of whole site of the primary tumour and metastatic sites (outside pulmonary sites) can take place before or after the high dose consolidation chemotherapy
Other Name: Radiotherapy of primary tumour/metastatic sites




Primary Outcome Measures :
  1. Anti-tumour effect of the treatment strategy assessed by the number of patients event-free survival (EFS) at 18 months [ Time Frame: 18 months after inclusion of the last patient ]
    EFS is defined as the time from inclusion date to the first documentation of progression, distant disease, second cancer or death (or last news for patients free of event). The event free survival is estimated by Kaplan-Meier method.


Secondary Outcome Measures :
  1. Anti-tumour effect of the dose-intensified induction chemotherapy assessed by the response rate of patients [ Time Frame: week 19-20 = Response Evaluation 2 (RE2) ]
    Number of patients with complete response (CR) / partial response (PR) eligible for consolidation phase

  2. Anti-tumour effect of the dose-intensified induction chemotherapy assessed by the number of patients eligible for consolidation phase [ Time Frame: week 19-20 = RE2 ]

    Number of patients eligible for consolidation phase have good response after induction phase :

    • complete remission on primary tumour and on metastatic sites or
    • very good disease response defined by:

      • complete or partial response according to RECIST 1.1 criteria on primary lesion
      • complete or very good partial response (> 90 %) in case of RECIST 1.1 criteria on metastatic sites AND
      • complete metabolic response in case of metastatic visceral and/or bone/bone marrow lesions, or very good partial response according to investigator's judgment AND
      • in case of bone marrow involvement, bone marrow free of disease on at least one biopsy and two punctures at different sites at RE1 (evaluation after 4 cycles VDC-IE), RE2 (evaluation after 2x4 cycles VDC-IE or 4 cycles VDC-IE+4 cycles TEMIRI), or at the latest RE3 evaluation (evaluation after local treatment).

  3. Overall survival (OS) is assessed by the number of patients still alive at the end of the three years of treatment [ Time Frame: 3 years = Response Evaluation End-Of-Treatment (EOT RE) ]
    The overall survival (OS) is estimated by Kaplan-Meier method.

  4. 3-years event-free survival (EFS) is assessed by the number of patients without any event at the end of treatment phase [ Time Frame: 3 years = EOT RE ]
    EFS is defined as the time from inclusion date to the first documentation of progression, distant disease, second cancer or death (or last news for patients free of event). The event free survival is estimated by Kaplan-Meier method.

  5. Number of patients with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: week 19-20 = RE2 ; week 27-28 = Response Evaluation 3 (RE3); 3 years = EOT RE ]
    Number of patients with treatment-related adverse events using the NCI CTCAE version 4.03 to graduate the severity of adverse events

  6. Number of patients with treatment-related toxicities on laboratory data as assessed by CTCAE v4.03 of the different phases of treatment [ Time Frame: week 19-20 = RE2 ; week 27-28 = RE3; 3 years = EOT RE ]
    Number of patients with treatment-related toxicities on laboratory data using the NCI CTCAE version 4.03 to graduate the severity of toxicities

  7. 18F-FDG PET evaluation efficacy assessed by primary tumour uptake [ Time Frame: study inclusion, after week 8 (RE1), after week18-19 (if VDC-IE) or week19-20 (if TEMIRI)=RE2, after local treatment ≤week30 (RE3), from week31 (=RE4), 3 years = EOT RE ]
    Efficacy assessed by primary tumour uptake (Standardized Uptake Value max at 18F-FDG PET)

  8. 18F-FDG PET evaluation efficacy assessed by metabolic tumour volume (MTV) [ Time Frame: study inclusion, after week 8 (RE1), after week18-19 (if VDC-IE) or week19-20 (if TEMIRI)=RE2, after local treatment ≤week30 (RE3), from week31 (=RE4), 3 years = EOT RE ]
    Efficacy assessed by metabolic tumour volume (MTV at 18F-FDG PET)

  9. Percentage of circulating tumour cells in blood and bone marrow to correlate with patient outcome (EFS). Ancillary study [ Time Frame: study inclusion, and/or during Procedure=surgery (if done) either after week 19-20=RE2 or after PBSC infusion=RE4 ]
    sample collected : primary tumour and metastatic site (if possible)

  10. Percentage of circulating tumour cells in blood and bone marrow to correlate with patient outcome (EFS). Ancillary study [ Time Frame: study inclusion, at each evaluation time (RE1=week8 to Response Evaluation before maintenance therapy (RE5=<week38)), every 3 months during 2 years maintenance therapy, at End of Treatment ]
    sample collected : blood

  11. Percentage of circulating tumour cells in blood and bone marrow to correlate with patient outcome (EFS). Ancillary study [ Time Frame: at diagnosis (before treatment), at 1st evaluation time (RE1=wk8 if bone marrow involvement at diagnosis), at RE2=week19-20 (or RE3=<week30), after PBSC infusion=RE4 or RE5=< week38 (if bone marrow involvement at diagnosis), at End of Treatment ]
    sample collected : bone marrow

  12. Comparison of transcriptomic profiles between those of primary disease and those of bone marrow metastases to determine if they are the same or not. Ancillary study [ Time Frame: study inclusion ]
    Investigation whether the cells from metastatic material harbour a unique transcriptomic signature compared to primary tumour cells : quantification of EWS-ETS transcript and EWS-ETS gene using Polymerase Chain Reaction (PCR) methods to determine the genomic EWS-ETS translocation loci



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. - Ewing tumour histologically or cytologically confirmed, harboring a specific transcript, and with extrapulmonary metastases.
  2. - Ewing tumour not previously treated.
  3. - Age between 2 and 50 years.
  4. - Measurable disease by cross sectional imaging (RECIST 1.1) or evaluable disease with functional metabolic, positron emission tomography scanner (PET SCAN) or other methods (e.g., cytology/histology).
  5. - General status compatible with the study treatments (LANSKY score ≥ 50%, or Karnofsky ≥ 50%, or Eastern Cooperative Oncology Group (ECOG) ≤ 2).
  6. - Adequate bone marrow function (not applicable in case of bone marrow disease).

    • Platelets ≥ 100 x 109 /L
    • Absolute Neutrophil Count (ANC) ≥ 1 x 109 /L
    • Hemoglobin ≥ 8g /dL.
  7. - Adequate liver function :

    • Aspartate Aminotransferase (AST) and Alanine Transferase (ALT) ≤ 5 x Upper Limit Normal (ULN)
    • Bilirubin conjugated fraction (BCF) ≤ 2 x Upper Limit Normal (ULN)
  8. - No absolute contra-indication of Busulfan-Melphalan if radiotherapy of the primary tumour is necessary.
  9. - Adequate cardiac and renal functions:

    • Creatinine < 1.5 of normal for age or clearance > 60 ml/min/1.73 m²;
    • Left Ventricular Ejection Fraction (LVEF) > 50% and/or shortening fraction > 28%.
  10. - No underlying disease contra-indicating the study treatments.
  11. - Patient likely compliant with the recommended study medical monitoring during and after treatments.
  12. - Patients of childbearing potential must agree to use adequate contraception for the duration of study treatments and up to 12 months for women and 6 months for men following completion of therapy.
  13. - Females of childbearing potential must have a negative serum β-human chorionic gonadotropin (HCG) pregnancy test within 10 days prior study inclusion, and/or urine pregnancy test within 48 hours before the first administration of the study treatment.
  14. - Patients covered by a health insurance system.
  15. - Patient, or patient's legal representative, informed and having signed the informed consent.

Exclusion Criteria:

  1. - Age below 2 or greater than 50 years.
  2. - Ewing tumour localized, or solely with pleural and/or lung metastases.
  3. - Primary tumour localized to the spine.
  4. - Concomitant disease, particularly infectious disease, likely to interfere with patient's treatment.
  5. - History of cancer, according to investigator's judgment.
  6. - Life expectancy < 2 months.
  7. - Patient already included in another clinical trial with an investigational drug.
  8. - Pregnant or breastfeeding patient.
  9. - Person deprived of liberty or under guardianship.
  10. - Patient likely unable to comply with the study medical monitoring for geographical, social or psychological reasons.

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): NCT03011528


Contacts
Layout table for location contacts
Contact: BOUFFIER Emmanuelle +33(0)156 245 765 emmanuelle.bouffier@curie.fr
Contact: Christine FOULON, Proj. Manag. +33(0)147 111 654 christine.foulon@curie.fr

Locations
Layout table for location information
France
Chr Felix Guyon Not yet recruiting
La Réunion, Saint Denis, France, 97400
Principal Investigator: Yves REGUERRE, MD         
Bordeaux Chu Recruiting
Bordeaux, France, 33076
Contact: Cécile VERITE-GOULARD, MD    +33(0)556795430    cecile.verite@chu-bordeaux.fr   
CHU Grenoble Alpes Not yet recruiting
Grenoble, France, 38043
Principal Investigator: Dominique PLANTAZ, P         
LILLE Centre Oscar Lambret Recruiting
Lille, France, 59000
Contact: Cyril LERVAT, MD    +33(0)320295935    c-lervat@o-lambret.fr   
LYON Centre Léon Bérard Recruiting
Lyon, France, 69000
Contact: Nadège CORRADINI, MD    +33(0)469166572    nadege.corradini@lyon-unicancer.fr   
Marseille Chu Not yet recruiting
Marseille, France, 13000
Contact: Jean-Claude GENTET, MD    +33(0)491386821    jcgentet@ap-hm.fr   
CHRU Montpellier - Hôpital A. de Villeneuve Recruiting
Montpellier, France, 34295
Principal Investigator: Laure SAUMET, MD         
Nantes Chu Recruiting
Nantes, France, 44000
Contact: Estelle THEBAUD, MD    +33(0)240083810    estelle.thebaud@chu-nantes.fr   
PARIS Institut Curie Recruiting
Paris, France, 75005
Contact: Valérie LAURENCE, MD    +33(0)1 44 32 42 07    valerie.laurence@curie.fr   
PARIS Trousseau Recruiting
Paris, France, 75012
Contact: Marie-Domnique TABONE, MD    +33(0)144736062    marie-dominique.tabone@aphp.fr   
CHU Hôpital Sud Not yet recruiting
Rennes, France, 35056
Principal Investigator: Sophie TAQUE, MD         
Strasbourg Chu Recruiting
Strasbourg, France, 67098
Contact: Natacha ENTZ-WERLE, MD    +33(0)388128072    natacha.entz-werle@chu-strasbourg.fr   
Toulouse Chu Recruiting
Toulouse, France, 31059
Contact: Marie-Pierre CASTEX, MD    +33(0)534558610    castex.mp@chu-toulouse.fr   
TOULOUSE Institut Claudius Regaud Recruiting
Toulouse, France, 31059
Contact: Christine CHEVREAU, MD    +33(0)531155151    chevreau.christine@iuct-oncopole.fr   
NANCY Institut de Cancérologie de Lorraine Not yet recruiting
Vandoeuvre les Nancy, France, 54519
Contact: Maria RIOS, MD    +33(0)383598358    m.rios@nancy.unicancer.fr   
Nancy Chu Recruiting
Vandoeuvre-les-Nancy, France, 54511
Contact: Ludovic MANSUY, MD    +33(0)383154734    l.mansuy@chu-nancy.fr   
VILLEJUIF Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Nathalie GASPAR, MD    +33(0)142114166    nathalie.gaspar@gustaveroussy.fr   
Sponsors and Collaborators
Institut Curie
UNICANCER
Investigators
Layout table for investigator information
Principal Investigator: Valérie LAURENCE, MD Institut Curie
Principal Investigator: Nadège CORRADINI, MD Institut d'Hématologie et d'Oncologie Pédiatrique

Layout table for additonal information
Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT03011528     History of Changes
Other Study ID Numbers: IC 2015-13 CombinaiR3
First Posted: January 5, 2017    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma, Ewing
Sarcoma
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Melphalan
Busulfan
Celecoxib
Temozolomide
Ifosfamide
Isophosphamide mustard
Doxorubicin
Liposomal doxorubicin
Irinotecan
Etoposide
Etoposide phosphate
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists