Multicentre, Randomised, Phase 2 Trial of Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (Metastatic Osteosarcoma at Diagnosis or Localised Disease With Poor Histological Response)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- UNICANCER
- 入组人数
- 60
- 试验地点
- 62
- 主要终点
- Compare event-free survival in the treatment arms
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Experimental arm
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
干预措施: Mifamurtide (Drug)
Control 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
干预措施: EI or M-API regimen depending on patient age (Combination Product)
Experimental arm
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
干预措施: EI or M-API regimen depending on patient age (Combination Product)
结局指标
主要结局
Compare event-free survival in the treatment arms
时间窗: Expected average duration of 3 years from randomization
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)
次要结局
- Compare actual and planned cumulative dose and dose intensity of mifamurtide(Up to 36 weeks from randomization (until end of treatment))
- Compare overall survival in the treatment arms(Up to 10 years from randomization)
- Compare the incidence of adverse events in the treatment arms(Up to 40 weeks from randomization (4 weeks after end of treatment))