Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (SARCOME13)
Osteosarcoma
About this trial
This is an interventional treatment trial for Osteosarcoma focused on measuring Bone, Neoplasm, bone tissue, Acetylmuramyl-Alanyl-Isoglutamine
Eligibility Criteria
Registration Criteria:
- All newly diagnosed, biopsy-proven, high-grade osteosarcoma, whatever the initial extension of the disease
- Age >2 years and ≤50 years;
- Normal haematological, renal, cardiac and hepatic functions
Planned neoadjuvant chemotherapy as follows:
- Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients ≤25 years
- Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years
- Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure
- Affiliation to a social insurance regimen
Inclusion Criteria:
- Patient with a histologically proven, confirmed by experts pathologists panel (before surgery at the latest), high-grade osteosarcoma
- Registered at diagnosis into the study
- Primary tumour resected after pre-operative chemotherapy
Osteosarcoma classified as high risk because of at least one risk factor:
- presence of distant metastases or skip metastases at diagnosis
- and/or poor histological response to pre-operative chemotherapy (>10% residual viable cells on the analysis of the primary tumour surgical specimen)
Pre-operative chemotherapy combining
- Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients ≤25 years
- Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years
Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to randomisation:
- Absolute neutrophil count ≥1.0 x 10⁹/L
- Platelets ≥100 x 10⁹/L
- Haemoglobin ≥8.0 g/mL
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) in the absence of liver metastases or ≤5 x ULN in the presence of liver metastases
- Total Bilirubin ≤2 x ULN (except Gilbert Syndrome: <3.0 mg/dL) or Total Bilirubin ≤5.0 x ULN in the presence of liver metastases
- Creatinine clearance ≥60 mL/min/1.73 m² according to the Schwartz or Cockcroft formula according to patient's age
- 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
- Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses.
- Patient fit to undergo protocol treatment and follow-up
- Affiliation to a social insurance regimen
Exclusion Criteria:
- Low grade osteosarcoma, parosteal or periosteal osteosarcoma
- Prior history of other malignancies other than study disease (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.
- Osteosarcoma with multiple metastases for whom complete removal is not expected to be feasible even after shrinkage with chemotherapy
- Progressive disease at any site under initial chemotherapy, confirmed before randomisation time, and not totally resected during surgery
- Any medical condition precluding treatment with protocol chemotherapy
- Fractional Shortening <28% or left ventricular ejection fraction (LVEF) 50% before treatment (only for API post-operative chemotherapy) by echocardiogram or multigated acquisition (MUGA) scan
- Pregnancy or breast-feeding
- Hypersensitivity to the active substance or to any of the excipients
- Concurrent use of immunodepressive treatment such as cyclosporine, tacrolimus or other calcineurin inhibitors
- Concurrent use with high-dose non-steroidal anti-inflammatory drugs (NSAIDs, cyclooxygenase inhibitors)
- Inflammatory or auto-immune disease, allergy or asthma requiring a chronic use of steroid treatment that cannot be stopped.
- Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- 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.
Sites / Locations
- CHU Amiens-Picardie - Service d'oncologie hématologie pédiatriqueRecruiting
- CHU d'Angers - Service d'oncologie pédiatriqueRecruiting
- Institut Bergonié - Service d'oncologie médicaleRecruiting
- CHU de Caen - Service d'oncologie hématologie pédiatriqueRecruiting
- CHU de Grenoble - Service d'oncologie hématologie pédiatriqueRecruiting
- Centre Oscar Lambret - Unité d'onco-pédiatrieRecruiting
- Centre Léon Bérard - IHOPERecruiting
- Centre Léon Bérard - Service d'oncologie médicaleRecruiting
- Hôpital de la Timone - service d'oncologie médicaleRecruiting
- Hôpital de la Timone - Service d'oncologie pédiatriqueRecruiting
- CHU Arnaud de Villeneuve - Onco-hématologie pédiatriqueRecruiting
- Institut régional du Cancer de Montpellier - Service d'oncologie médicaleRecruiting
- CHU de Nantes - Service d'oncologie hématologie pédiatriqueRecruiting
- CHU de Nice - Service d'oncologie hématologie pédiatriqueRecruiting
- Institut Curie - Service d'oncologie médicaleRecruiting
- Hôpital Armand Trousseau - Service d'hématologie et d'oncologie pédiatriqueRecruiting
- Hôpital CochinRecruiting
- Institut Curie - Service d'oncologie pédiatriqueRecruiting
- Centre Eugène Marquis - Service d'oncologie médicaleRecruiting
- Hôpital Charles Nicolle - Hémato-Immuno-Oncologie PédiatriqueRecruiting
- Institut de Cancérologie de l'Ouest (Site René Gauducheau) - Service d'oncologie médicaleRecruiting
- Hôpital de Hautepierre - Onco-hématologie adulteRecruiting
- Hôpital Hautepierre - Onco-hématologie pédiatriqueRecruiting
- CHU Toulouse - Hôpital des Enfants - Service d'Hémato-Immuno-OncologieRecruiting
- Institut Claudius Regaud - service d'oncologie médicaleRecruiting
- CHU Bretonneau - Service d'oncologie médicaleRecruiting
- Hôpital Clocheville - Hématologie et oncologie pédiatriqueRecruiting
- CHRU de Nancy - Onco-hématologie pédiatriqueRecruiting
- Institut de Cancérologie de Lorraine - Service d'oncologie médicaleRecruiting
- Institut Gustave Roussy - Service de cancérologie de l'enfant et de l'adolescentRecruiting
- Institut Gustave Roussy - Service d'oncologie médicaleRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Control arm
Experimental arm
Post-operative chemotherapy alone (EI or M-API regimen depending on patient age) : M-API regimen (≤25 years) : Doxorubicin 60 mg/m², Day 1 Ifosfamide 3 g/m² Day 1 and 2 Cisplatin 100 mg/m², Day 2 EI regimen (26-50 years) : Etoposide 75 mg/m²/d, Day 1-4 Ifosfamide 3 g/m²/d, Day 1-4
Post-operative chemotherapy (EI or M-API regimen) combined with Mifamurtide 2 mg/m² twice weekly post-randomisation for 12 weeks then weekly for 24 weeks