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First-line treatment of Ewing tumours with primary extrapulmonary dissemination in patients from 2 to 50 years

Phase 1
Conditions
First-line treatment of Ewing tumours with primary extrapulmonary dissemination in patients from 2 to 50 years
MedDRA version: 19.0Level: PTClassification code 10055101Term: Bone cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2016-000981-46-FR
Lead Sponsor
INSTITUT CURIE
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
45
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 PET scan or other methods (e.g., cytology/histology).
5 - General status compatible with the study treatments (Lansky = 50%, or Karnofsky = 50%, or ECOG = 2).
6 - No absolute contra-indication of Busulfan-Melphalan if radiotherapy of the primary tumour is necessary.
7 - Adequate cardiac and renal functions:
oCreatinine < 1.5 of normal for age or clearance > 60 ml/min/1.73 m²;
oLeft Ventricular Ejection Fraction (LVEF) > 50% and/or shortening fraction > 28%.
8 - No underlying disease contra-indicating the study treatments.
9 - Patient likely compliant with the recommended study medical monitoring during and after treatments.
10 - Patients of childbearing potential must agree to use adequate contraception for the duration of study treatments and up to 6 months following completion of therapy.
11 - Females of childbearing potential must have a negative serum ß-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.
12 - Patients covered by a health insurance system.
13 - Patient, or patient’s legal representative, informed and having signed the informed consent.

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Investigate the antitumor effect of this treatment strategy assessed by event-free survival (EFS) at 18 months. ;Secondary Objective: •Investigate the anti-tumour effect of the dose-intensified induction chemotherapy assessed by the response rate and the number of patients eligible for consolidation by high dose chemotherapy with autologous peripheral blood stem cell (PBSC) reinfusion after the dose-intensified induction chemotherapy.<br>•Investigate the 3-year outcome assessed by the overall survival (OS) and event-free survival (EFS) at 3 years.<br>•Investigate the safety profiles of the different phases of treatment.;Primary end point(s): 18-month event-free survival (EFS);Timepoint(s) of evaluation of this end point: 18 months (median duration of follow up)
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): •Response rate after the dose-intensified induction chemotherapy<br>•Number of patients eligible for the high-dose chemotherapy after the dose-intensified induction chemotherapy<br>•3-year overall survival (OS)<br>•3-year event-free survival (EFS)<br>•Rate and severity of toxicities assessed according to the NCI CTCAE 4.03 scale (through 30 days after study treatments discontinuation)<br>;Timepoint(s) of evaluation of this end point: Timepoint are given in months after trial initiation.<br><br>•Response rate after the dose-intensified induction chemotherapy : 50 months<br>•Number of patients eligible for the high-dose chemotherapy after the dose-intensified induction chemotherapy : 50 months<br>•3-year overall survival (OS) : 72 months<br>•3-year event-free survival (EFS) : 72 months<br>•Rate and severity of toxicities assessed according to the NCI CTCAE 4.03 scale (through 30 days after study treatments discontinuation) : 72 months
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