Phase 3 Prospective, Randomized, Blinded, and Controlled Investigation of HepaSphere/QuadraSphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 235
- 试验地点
- 45
- 主要终点
- Median Overall Survival
研究概览
简要总结
The purpose of this study is to evaluate overall survival in patients diagnosed with hepatocellular cancer (HCC) treated with HepaSphere/QuadraSphere Microspheres loaded with chemotherapeutic agent doxorubicin compared to conventional transarterial chemoembolization with particle PVA, lipiodol, and doxorubicin.
详细描述
This phase three, interventional, and prospective study consists of a patient population that has advanced liver cancer (hepatocellular cancer [HCC]) that cannot be removed by standard therapies such as surgical removal, liver transplant, and/or ablation.
Embolics and drug eluting embolics are being used by interventional radiologists to try and shrink or kill the tumor area.
Patients that met eligibility criteria, wanted to participate in the study, and signed the informed consent form (ICF) made up the study subject population. Subjects were randomized on a 1:1 basis (subjects were blinded to arm they were randomized to).
Post randomization and within four weeks of the first chemoembolization procedure all subjects had a baseline MRI. Following, the first chemoembolization procedure (hqTACE or cTACE) or 'cycle' was completed. Subjects can (per protocol) receive up to 3 TACE cycles. Within 4 weeks after any TACE cycle, an MRI and labs should be conducted/collected to evaluate disease status (reduction vs progression) and measure treated lesions. Any residual disease that is present after after the first TACE will undergo the next TACE cycle (maximum of three). However, if the liver MRI shows a complete response (absence of HCC) then no additional TACE procedures are performed and the subject is followed for survival.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Participants are blinded to the treatment they are randomized to (cTACE or hqTACE). Central Reviewers (two interventional radiologists) will evaluate study participant's liver MRIs to assess the tumor response. The Central Reviewers will be blinded to the treatment the participant received.
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
- •Patients must meet all of the following inclusion criteria in order to be entered into the study:
- •Age 18 or older
- •Patient has signed informed consent
- •Patient must have a diagnosis of hepatocellular cancer confirmed by at least one of the following:
- •i. Histological confirmation ii. Magnetic resonance imaging (MRI) result with early enhancement and delayed enhancement washout of at least one solid liver lesion > 1 cm. Patient must also have evidence of cirrhosis or have chronic hepatitis B.
- •iii. Contrast enhanced computed tomography (CT) with early enhancement and delayed enhancement washout of at least one solid liver lesion > 1cm. Patient must also have evidence of cirrhosis or have chronic hepatitis B.
- •d. Patient must not be suitable for treatment by resection or percutaneous ablation at time of study entry.
- •Patients not suitable for ablation due to lesion location may be enrolled
- •e. Patient MUST meet at least ONE of the following criteria:
- •i. Stage Child-Pugh B 7 ii. Recurrent HCC iii.Performance status ECOG 1
- •f. Patient has a life expectancy of at least 6 months
- •g. Absence of occlusive thrombus to the main portal trunk
排除标准
- •If patients meet any of the following criteria they may not be entered into the study:
- •Current or previous treatment with chemo- or radiation therapy or sorafenib
- •Previous treatment with any form of transarterial embolization for HCC
- •Patients with current or history of any other cancer except non-melanomatous skin cancer
- •Female patients who are pregnant, breastfeeding, or premenopausal and not using an effective method of contraceptive
- •Performance status ECOG > 2
- •Child-Pugh scores >7
- •Active gastrointestinal bleeding
- •Evidence of uncorrectable bleeding diathesis
- •Extra-hepatic spread of the HCC
- •Total Bilirubin > 3 mg/dL
- •>50% tumor involvement of the liver
- •Infiltrative or diffuse HCC
- •Encephalopathy not adequately controlled medically
- •Presence of ascites not controlled medically
- •Presence of medically relevant localized or systemic infection, other than hepatitis B, C, D, E or G
- •Any contraindication for MRI (eg. metallic implants)
- •Allergy to contrast media that cannot be managed with prophylaxis
- •Allergy to iodized oil
- •Any contraindication to arteriography
- •Any contraindication for doxorubicin administration, including the following:
- •i. White Blood Cell count (WBC) <3000 cells/mm₃
- •ii. Absolute Neutrophil <1500 cells/mm₃
- •iii. Cardiac ejection fraction <50%
- •iv. Other condition deemed exclusionary by physician
- •u. Any contraindication for hepatic embolization, including the following:
- •i. Porto-systemic shunt, or an arteriovenous shunt that cannot be adequately closed prior to chemoembolization
- •ii. Hepatofugal blood flow
- •iii. Serum creatinine > 2mg/dL
- •iv. Uncorrectable impaired clotting
- •Platelet <50,000/mm₃
- •International Normalized Ratio (INR) > 1.4
- •Activated Prothrombin Time (aPTT) less than 21 or greater than 40
- •v. AST > 5X upper limit of normal for lab
- •vi. ALT > 5X upper limit of normal for lab
结局指标
主要结局
Median Overall Survival
时间窗: 2 years
Median overall survival will be calculated using the Intent-to-Treat (ITT) population in each treatment arm when the last subject has completed two years of follow up after their first study TACE procedure. Per protocol, study subjects were followed for survival until death or deemed lost to follow up. All deaths are reported within safety.
次要结局
- Objective Response Rates (ORR)(Study was terminated early so analysis of additional outcome(s) were not possible.)