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- Conditions
- Patients =50 years old with high-risk osteosarcoma (defined as metastatic osteosarcoma at diagnosis or localised osteosarcoma with poor histological response) after pre-operative chemotherapy and surgery of the primary tumour and lung metastases (if applicable).Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001165-24-FR
- Lead Sponsor
- ICANCER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 390
These criteria must be met at diagnosis for registration in the study:
1. All newly diagnosed, biopsy-proven, high-grade osteosarcoma, whatever the initial extension of the disease
2. Age =50 years;
3. Normal haematological, renal, cardiac and hepatic functions
4. Planned neoadjuvant chemotherapy as follows:
a. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients = 25 years
b. Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years
5. Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure
6. Affiliation to a social insurance regimen
INCLUSION CRITERIA FOR THE RANDOMISATION
1. Patient with a histologically proven, confirmed by expert pathologists panel (before surgery at the latest), high-grade osteosarcoma
2. Registered at diagnosis into the study
3. Primary tumour resected after pre-operative chemotherapy
4. Osteosarcoma classified as high risk because of at least one risk factor:
a. presence of distant metastases or skip metastases at diagnosis
b. and/or poor histological response to pre-operative chemotherapy (>10% residual viable cells on the analysis of the primary tumour surgical specimen)
5. Pre-operative chemotherapy combining
a. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients = 25 years
b. Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years
6. Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to randomisation :
a. Absolute neutrophil count = 1 x 109/L
b. Platelets = 100 x 109/L
c. Haemoglobin = 8.0 g/mL
d. ALT/AST = 2.5 x ULN in the absence of liver metastases or = 5.0 x ULN in the presence of liver metastases
e. Total bilirubin = 2 x ULN (except Gilbert Syndrome : < 3.0 mg/dL) or = 5.0 x ULN in the presence of liver metastases
f. Creatinine clearance = 60 mL/min/1.73 m² according to the Schwartz or Cockroft formula according to patient’s age
7. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 7 days prior to randomisation
8. Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses.
9. Patient fit to undergo protocol treatment and follow-up
10. Affiliation to a social insurance regimen
Are the trial subjects under 18? yes
Number of subjects for this age range: 277
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 113
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
NON-INCLUSION CRITERIA FOR THE RANDOMISATION
1. Low grade osteosarcoma, parosteal or periosteal osteosarcoma
2. Prior history of other malignancies other than osteosarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years.
3. Osteosarcoma with multiple metastases for whom complete removal is not expected to be feasible even after shrinkage with chemotherapy
4. Progressive disease at any site under initial chemotherapy, confirmed before randomisation time, and not totally resected during surgery
5. Any medical condition precluding treatment with protocol post-operative chemotherapy
6. Fractional Shortening < 28% or LVEF< 50% before treatment (only for API post-operative chemotherapy) by echocardiogram or Muga scan
7. Pregnancy or breast-feeding
8. Hypersensitivity to the active substance or to any of the excipients
9. Concurrent use of immunodrepressive treatment such as ciclosporine, tacrolimus or other calcineurin inhibitors
10. Concurrent use with high-dose non-steroidal anti-inflammatory drugs (NSAIDs, cyclooxygenase inhibitors)
11. Inflammatory or auto-immune disease, allergy or asthma requiring a chronic use of steroid treatment that cannot be stopped.
12. Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
13. Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method