Multicentre, Randomised, Controlled, Open-label Study Comparing the Efficacy and Safety of Doxorubicin Transdrug™ to Best Standard of Care in Patients With Advanced Hepatocellular Carcinoma. ReLive Study.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 397
- 试验地点
- 69
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this phase III study is to determine whether Doxorubicin Transdrug (DT) is effective in the treatment of patients suffering from advanced Hepatocellular Carcinoma (HCC) after failure or intolerance to Sorafenib. Patients with HCC with or without cirrhosis and with good liver functions are eligible. Only those who can not benefit from treatment for which efficacy is demonstrated are eligible.
These patients are usually proposed either best standard of care (BSC) or participation to clinical trials. Patients eligible for the RELIVE study will receive either DT at 20 mg/m2 or DT at 30 mg/m2 or the BSC.
详细描述
Doxorubicin-Transdrug™ (DT) is a nanoparticle formulation of doxorubicin.In in vitro and in vivo models, DT was shown to overcome the multidrug resistance (MDR) and to be more effective than doxorubicin on both sensitive and resistant tumour models and in particular in the X/myc bi-transgenic MDR murine model of HCC.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-breast feeding female;
- •Aged ≥ 18 years;
- •Patient with:
- •advanced HCC (BCLC-C according to BCLC staging classification) having progressed under Sorafenib therapy or intolerant to Sorafenib, or;
- •intermediate HCC (BCLC-B) non eligible or non responders to transarterial chemoembolization (TACE), and having progressed under or intolerant to Sorafenib therapy
- •Patients with porta hepatis lymph nodes, extrahepatic metastases, or portal/suprahepatic vein thrombosis without extension in inferior/superior vena cava, are eligible;
- •HCC diagnosed according to the American Association for Study of Liver Diseases (AASLD) and/or European Association for the Study of the Liver (EASL) criteria:
- •Radiological Criteria applicable in cirrhotic liver:
- •Nodule ≥ 10 mm: one imaging technique among MRI and CT-scan showing typical appearances for HCC defined as arterial enhancement and rapid washout in portal venous or delayed phase;
- •If appearance not typical for HCC on initial imaging: second contrast enhanced study (CT or MRI) showing typical appearances for HCC defined as arterial enhancement and rapid wash-out in portal venous or delayed phase;
- •And/Or cyto-histology criteria (e.g. in case of atypical lesions for HCC at imaging, absence of cirrhosis);
- •Without cirrhosis or with a non decompensated cirrhosis (Child-Pugh score from A5 to B7 included);
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
- •Laboratory tests as follows:
- •Platelets ≥ 50,000 /mm3
- •Neutrophil count ≥ 1000/mm3
- •Hemoglobin ≥ 10g/dL
- •Serum transaminases < 5 upper limit normal (ULN) (NCI/common toxicity criteria (CTC) grades 0, 1, or 2)
- •Alkaline phosphatases < 5 ULN (NCI/CTC grades 0, 1, or 2)
- •Serum bilirubin < 35 micromolar (µM)/L (or 2.0 mg/dL);
- •Signed and dated written informed consent form.
排除标准
- •Cirrhosis with a Child-Pugh score B8-C15;
- •Untreated chronic hepatitis B;
- •Patients eligible for curative treatments (transplantation, surgical resection, percutaneous treatment);
- •Patients eligible for palliative treatments with demonstrated efficacy: TACE, Sorafenib; Patients who failed to Sorafenib treatment or intolerant to sorafenib are eligible and can be included if Sorafenib has been stopped at least 2 weeks before randomization;
- •Prior history of malignancy with the exception of adequately treated basal cell carcinoma or in situ cervical cancer in complete remission since five years at least;
- •HCC developed on transplanted liver;
- •HIV infection;
- •Risk of variceal bleeding;
- •Oxygen saturation (SaO2) < 95%;
- •Presence of a significant acute or chronic respiratory disease defined as NCI/CTCAE > grade 2;
- •Presence of recent (< 6 months) or current cardiac failure (class III or IV New York Heart Association (NYHA) classification), recent (< 6 months) acute coronary syndrome, clinically significant ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke, myocardial infarction (MI)...);
- •Prior cumulative dose of 300 mg/m² of doxorubicin or equivalent;
- •Patients currently treated with immunosuppressive agents that cannot be stopped;
- •Patients whose medical or surgical conditions are unstable and may not allow the study completion or compliance, and specially patients with uncontrolled diabetes;
- •Uncontrolled systemic infection;
- •Patients with a life expectancy of less than 2 months;
- •Patients who have received an experimental drug in another clinical trial in the last 30 days prior to randomization in the present clinical trial;
- •Women of child-bearing age who are unwilling or unable to use an effective contraception method during the study treatment period and for 6 months after the last administration of study drug, and their male partner(s) refusing to use a condom (if applicable);
- •Men who are unwilling or unable to use a condom during the study treatment period and for 6 months after the last administration of study drug, and their female partner(s) refusing to use one of the appropriate effective contraception methods (if applicable);
- •Patients unwilling or unable to comply with protocol requirements and scheduled visits.
研究组 & 干预措施
Doxorubicin Transdrug (DT) at 20 mg/m2
DT will be infused over 6 hours through the intravenous (IV) route at dose of 20 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity
干预措施: Doxorubicin 20 mg/m2 (Drug)
Doxorubicin Transdrug (DT) at 30 mg/m2
DT will be infused over 6 hours through the IV route at dose of 30 mg/m2 on Day 1 and will be repeated every 4 weeks until disease progression or unacceptable toxicity
干预措施: Doxorubicin 30 mg/m2 (Drug)
Best Standard of Care
Patients randomized in the control group will receive treatment according to the investigator's choice, until disease progression or unacceptable toxicity
干预措施: Best Standard of Care (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Time from date of randomization to the date of death from any cause with initial assessment up to 24 months and follow-up assessment up to 45 months.
OS is defined as the time from date of randomization to the date of death from any cause.
次要结局
- Progression-free Survival (PFS)(Time from date of randomization to date of first documented progression or death from any cause, which ever came first, assessed up to 20 months.)
- Objective Response Rate (ORR)(Time from date of first treatment cycle to date of last cycle of treatment for the full duration of study treatment up to 24 months.)