Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 18
- 主要终点
- Rate of Hepatic Progression Free Survival at 24 Months
研究概览
简要总结
Determine wether 24 months treatment with everolimus prolongs progression free survival rate (based on a central assessment) after embolisation ou chemoembolisation for liver metastases.
- H0 a 24 months progression free survival rate less than 35% is unacceptable
- H1 a 24 months progression free survival rate greater than 35% would show that everolimus treatment is beneficial, the expected 24 months progression free survival rate being 50%
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Well differentiated (grade 1 and 2 according to WHO classification 2010 appendix 2), histologically-proven endocrine tumor of the gastrointestinal tract (TENpath review mandatory),
- •Measurable liver metastasis (or metastases) as defined in RECIST v1.1 that are unresectable and inaccessible to radiofrequency ablation-type local treatment
- •Hepatic arterial embolization or chemoembolization indicated for tumor size reduction, confirmed in an multidisciplinary team (MDT) meeting, due to the progressive nature of the liver metastases (morphological progression during the past 12 months as defined in RECIST v1.1)
- •Age ≥ 18 years
- •WHO performance status ≤ 2
- •No contraindications to embolization or chemoembolization or everolimus
- •Satisfactory laboratory assessments:Neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, Hb > 10 g/dL, serum bilirubin ≤ 1.5 x the upper limit of normal (ULN), INR < 1.3 (or < 3 for patients on anticoagulant therapy) ALT and AST ≤ 5 x ULN, creatinine ≤ 1.5 x ULN, fasting serum cholesterol ≤ 300 mg/dL or 7.75 mmol/L and triglycerides ≤ 2.5 x ULN (if either or both of these limits are exceeded, the patient may only be included into the study after institution of appropriate lipid-lowering therapy)
- •Complete resolution of toxic effects of any prior treatments, or persistence at grade 1 at most (CTCAE version 4.0)
- •Minimum time since previous treatment: 28 days
- •Patient has been informed and has signed an informed consent form, after verification of the eligibility criteria
- •Patient covered by a French national health insurance scheme
排除标准
- •Duodenopancreatic neuroendocrine tumor
- •Poorly differentiated and/or grade 3 endocrine tumor,
- •Embolization or chemoembolization indicated for symptomatic control only
- •Prior hepatic TACE or embolization
- •Prior treatment with an mTOR inhibitor (somatostatin analogs to control secretion are permitted)
- •Symptomatic bone metastasis (or metastases)
- •Any uncontrolled progressive disease: hepatic failure, renal failure, respiratory failure, NYHA class III-IV congestive heart failure, unstable angina, myocardial infarction, significant arrhythmia
- •Interstitial lung disease
- •Uncontrolled diabetes, defined by HbA1c > 8%
- •Chronic corticosteroid or immunosuppressant therapy
- •Hypersensitivity to everolimus, other rapamycin derivatives, or one of the excipients
- •Major surgery, open biopsy, or significant traumatic lesion during the 28 days prior to starting the investigational treatment Incompletely healed wound or foreseeable need for major surgery during the study
- •Contraindication to vascular occlusion procedures: Portal thrombosis, biliodigestive anastomosis
- •Malignancy during the past 5 years, with the exception of curatively treated basal cell skin carcinoma or in situ cervical cancer
- •Foreseeable non-compliance
- •Medical, geographic, sociological, psychological, or legal situation that would preclude the patient from completing the study or signing an informed consent form
- •Pregnant or breast-feeding women
- •Men or women of child-bearing potential not using effective contraception
- •Concurrent participation in another investigational study that could affect the primary endpoint of this study
研究组 & 干预措施
embolization or chemoembolization plus everolimus
After 2 sessions of embolization with microsphere of 100 to 500 µm or chemoembolization with 100 mg of doxorubicine and 10 ml of lipiodol, administered every day, 10 mg of everolimus during 24 months or until progression (hepatic and other site).
干预措施: Everolimus (Drug)
embolization or chemoembolization plus everolimus
After 2 sessions of embolization with microsphere of 100 to 500 µm or chemoembolization with 100 mg of doxorubicine and 10 ml of lipiodol, administered every day, 10 mg of everolimus during 24 months or until progression (hepatic and other site).
干预措施: embolization (Device)
embolization or chemoembolization plus everolimus
After 2 sessions of embolization with microsphere of 100 to 500 µm or chemoembolization with 100 mg of doxorubicine and 10 ml of lipiodol, administered every day, 10 mg of everolimus during 24 months or until progression (hepatic and other site).
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Rate of Hepatic Progression Free Survival at 24 Months
时间窗: Up to 24 months
Hepatic progression free survival rate as defined in RECIST 1.1 (with death considered as progression) during the 24 months of treatment with everolimus. Progression-free survival rate (PFS) (based on the investigator) according to RECIST v1.1 according to RECIST v1.1 will be defined as the time from the date of inclusion to the date of hepatic progression or death (due to any cause). For patients who are alive with no hepatic progression, it will be defines as the time from the date of inclusion and the date of the last tumor assessment.
次要结局
- Progression-free Survival (Hepatic or Not)(From randomization until the date of first progression (clinical or radiological) or death from any cause whichever came first, assessed up to 3 years)
- Overall Survival(From randomization until death or last news for alive patients)