Metformin as Maintenance Therapy in Patients With Bone Sarcoma and High Risk of Relapse
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Event Free Survival
研究概览
简要总结
Primitive bone sarcoma are rare tumors with low options of therapy for patient treatment.
- OSTEOSARCOMA VERY POOR RESPONDER COHORT. Necrosis on primitive localized osteosarcoma represents one of the principal prognostic factors. Nowadays, for localized osteosarcoma there is no maintenance therapy that have shown to be effective.
In ISG-OS1 study in patients with necrosis < 60% had an event free survival (EFS) at 3 yrs of 20% (Ferrari S ) in a more recent analysis (Tsuda Y 2020) patients with a necrosis <60% had a 3 y EFS of 35% . 2. OSTEOSARCOMA AND EWING'S SARCOMA AFTER FIRST RELAPSE Maintenance therapy after Complete Remission occurring after Ewing's sarcoma or osteosarcoma patients is not a standard rule.
These patients when free from disease, after first relapse, are more likely to face a second relapse. EFS at ONE YEAR after first relapse in osteosarcoma is shown in literature to be around 21% (Leary SE 2013) and 16% (Tirtei E 2017). The EFS at ONE YEAR after first relapse in Ewing's sarcoma is inferior to 20% (Barker 2005, Ferrari S 2015). A maintenance therapy with low toxicity in these high risk patients could be an option.
Metformin has been reported to a reduce the incidence of different type of cancer in diabetic patients. Metformin is well tolerated in diabetics an it is used in other conditions in non diabetic, as ovarian polycystic syndrome, metabolic syndrome and obesity. Metformin has been employed as chemoprevention related to its mechanism of action in breast cancer (NCT01101438 ) and in pediatric cancer together with chemotherapy (NCT01528046).
This study aim to explore the effectiveness of metformin (a low cost and well tolerated drug) as maintenance therapy in osteosarcoma and Ewing sarcoma patients at high risk of relapse.
详细描述
MATERIALS & METHODS The study is divided in two groups
- Group 1-Localized osteosarcoma that have reported a post neoadjuvant chemotherapy primary tumor necrosis ≤ 60% Metformin will be administrated for 3 years maximum or until progression disease or if G3 or G4 toxicity is verified.
37 patients as total population are necessary to evaluate a 3 yrs increase of EFS from 35% ( historical data Tsuda Y ) to 60%,
- Group 2 Osteosarcoma and Ewing sarcoma patients in Complete Remission after the first relapse.Metformin will be administrated for 3 years or until progression .
The Event Free Survival of this second group will be calculated at 1 yr with the aim of an increase of EFS from 20%(historical data) to 45%
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non metastatic osteosarcoma patients with necrosis ≤ 60 % in the end of post-operatory chemotherapy treatment (within 45 days.from the end of chemotherapy treatment).
- •Osteosarcoma or Ewing sarcoma patients free from the disease after first relapse (within 45 days.from the local surgery or 45 days from the end of chemotherapy treatment).
- •≥ 14 years.
- •Patient should not be participating in other clinical study.
- •Patients should be able to swallow.
- •Screening up to 30 days from the end of chemotherapy treatment or relapse.
- •Start therapy up to 30 days from the screening.
- •Normal renal function (creatinine <1,3 mg/L, clearance creatinine ≥ 70 ml/min) end liver function (total serum bilirubina <1,2 mg/dL, except Gilbert syndrome patients), AST e ALT <1,8 times the normal range value
排除标准
- •Type B diabetic patient
- •Metastatic patients
- •Patients with acute metabolic acidosis (lactic acidosis, diabetic ketoacidosis).
- •Patients with renal insufficiency (GFR < 70 ml/min).
- •Patients with acute conditions that could cause kidney alterations as dehydration, severe infection and shock.
- •Patients with hepatic insufficiency as acute alcohol intoxication and alcoholism.
- •Patients with medical conditions that could cause tissue hypoxia: decompensated heart failure, respiratory failure, recent myocardial infarction, shock.
- •Patient who does not meet the inclusion criteria
- •Pregnant and breastfeeding patients, or young women at childbearing age who cannot exclude the state of pregnancy (possibly excluded by serum pregnancy test (BhCG test), in accordance with the recommendations of the CTFG.
研究组 & 干预措施
Metformin
Metformin will be administrated according with patients body mass index (BMI). The study is divided into 2 groups.
- Group 1: Localized osteosarcoma that have presented a response ≤ 60% to the pre-operatory chemotherapy).
- Group 2: Osteosarcoma and Ewing sarcoma patients with complete remission after the first relapse.
干预措施: Metformin Hydrochloride (Drug)
结局指标
主要结局
Event Free Survival
时间窗: 3 years
Evaluate the event free survival (EFS) in osteosarcoma and Ewing sarcoma patients with high risk of relapse compared to the historical control
次要结局
- Metformin toxicity(3 years)
研究者
Alessandra Longhi,MD
Medical Doctor
Istituto Ortopedico Rizzoli