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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03643133
Other study ID # UC-0150/1704
Secondary ID 2017-001165-24
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date October 23, 2018
Est. completion date October 2033

Study information

Verified date February 2024
Source UNICANCER
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Trial evaluating the impact on efficacy of mifamurtide as add-on treatment to post-operative chemotherapy compared to post-operative chemotherapy alone in first-line treatment of patients with high-risk osteosarcoma (defined as metastatic osteosarcoma at diagnosis or localised osteosarcoma with poor histological response).


Description:

Multicentre, randomised, open-label, phase II trial, with 2 parallel groups. After pre-operative chemotherapy and surgery of the primary tumour and lung metastases (if applicable), patients presenting high-risk osteosarcoma (defined as metastatic osteosarcoma at diagnosis or localised osteosarcoma with poor histological response) will be randomised between 2 arms: - Control arm: post-operative chemotherapy alone (with regimens adapted to the age of patient) - Experimental arm : post-operative chemotherapy combined with mifamurtide This randomised trial is part of a study recruiting all patients ≤50 years old with a newly diagnosed high-grade osteosarcoma.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 60
Est. completion date October 2033
Est. primary completion date October 2024
Accepts healthy volunteers No
Gender All
Age group N/A to 50 Years
Eligibility Registration Criteria: 1. All newly diagnosed, biopsy-proven, high-grade osteosarcoma, whatever the initial extension of the disease 2. Age >2 years and =50 years; 3. Normal haematological, renal, cardiac and hepatic functions 4. Planned neoadjuvant chemotherapy as follows: 1. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients =25 years 2. 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: 1. Patient with a histologically proven, confirmed by experts 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: 1. presence of distant metastases or skip metastases at diagnosis 2. 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 1. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients =25 years 2. 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: 1. Absolute neutrophil count =1.0 x 10?/L 2. Platelets =100 x 10?/L 3. Haemoglobin =8.0 g/mL 4. 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 5. 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 6. Creatinine clearance =60 mL/min/1.73 m² according to the Schwartz or Cockcroft 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 Exclusion Criteria: 1. Low grade osteosarcoma, parosteal or periosteal osteosarcoma 2. 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. 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 chemotherapy 6. 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 7. Pregnancy or breast-feeding 8. Hypersensitivity to the active substance or to any of the excipients 9. Concurrent use of immunodepressive treatment such as cyclosporine, 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


Related Conditions & MeSH terms


Intervention

Drug:
Mifamurtide
48 doses overall over 36 weeks
Combination Product:
EI or M-API regimen depending on patient age
M-API regimen: One course of high-dose Methotrexate (optional) followed by 5 courses of API, every 21 days EI regimen : 5 course of EI, every 21 days

Locations

Country Name City State
France CHU Amiens-Picardie - Service d'oncologie hématologie pédiatrique Amiens
France CHU d'Angers - Service d'oncologie pédiatrique Angers
France Institut Bergonié - Service d'oncologie médicale Bordeaux
France CHU de Caen - Service d'oncologie hématologie pédiatrique Caen
France CHU de Grenoble - Service d'oncologie hématologie pédiatrique La Tronche
France Centre Oscar Lambret - Unité d'onco-pédiatrie Lille
France Centre Léon Bérard - IHOPE Lyon
France Centre Léon Bérard - Service d'oncologie médicale Lyon
France Hôpital de la Timone - service d'oncologie médicale Marseille
France Hôpital de la Timone - Service d'oncologie pédiatrique Marseille
France CHU Arnaud de Villeneuve - Onco-hématologie pédiatrique Montpellier
France Institut régional du Cancer de Montpellier - Service d'oncologie médicale Montpellier
France CHU de Nantes - Service d'oncologie hématologie pédiatrique Nantes
France CHU de Nice - Service d'oncologie hématologie pédiatrique Nice
France Hôpital Armand Trousseau - Service d'hématologie et d'oncologie pédiatrique Paris
France Hôpital Cochin Paris
France Institut Curie - Service d'oncologie médicale Paris
France Institut Curie - Service d'oncologie pédiatrique Paris
France Centre Eugène Marquis - Service d'oncologie médicale Rennes
France Hôpital Charles Nicolle - Hémato-Immuno-Oncologie Pédiatrique Rouen
France Institut de Cancérologie de l'Ouest (Site René Gauducheau) - Service d'oncologie médicale Saint-Herblain
France Hôpital de Hautepierre - Onco-hématologie adulte Strasbourg
France Hôpital Hautepierre - Onco-hématologie pédiatrique Strasbourg
France CHU Toulouse - Hôpital des Enfants - Service d'Hémato-Immuno-Oncologie Toulouse
France Institut Claudius Regaud - service d'oncologie médicale Toulouse
France CHU Bretonneau - Service d'oncologie médicale Tours
France Hôpital Clocheville - Hématologie et oncologie pédiatrique Tours
France CHRU de Nancy - Onco-hématologie pédiatrique Vandœuvre-lès-Nancy
France Institut de Cancérologie de Lorraine - Service d'oncologie médicale Vandœuvre-lès-Nancy
France Institut Gustave Roussy - Service d'oncologie médicale Villejuif
France Institut Gustave Roussy - Service de cancérologie de l'enfant et de l'adolescent Villejuif

Sponsors (1)

Lead Sponsor Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Compare event-free survival in the treatment arms Event-free survival defined as the time duration from randomisation to time of first event (loco-regional or distant relapse or progression, second malignancy, death from any cause) Expected average duration of 3 years from randomization
Secondary Compare overall survival in the treatment arms Overall survival defined as the time duration from randomisation to death, whatever the cause of death Up to 10 years from randomization
Secondary Compare actual and planned cumulative dose and dose intensity of mifamurtide Calculation of actual cumulative dose and dose intensity compared to the planned treatment administration schedule Up to 36 weeks from randomization (until end of treatment)
Secondary Compare the incidence of adverse events in the treatment arms Evaluation of toxicity (graded by NCI-CTCAE v4) Up to 40 weeks from randomization (4 weeks after end of treatment)
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