Treatment of Hepatocellular Carcinoma (HCC)by Selective Traditional Chemoembolization(TACE)Versus Selective TACE Via Microspheres Loaded With Doxorubicin: a Multicentre,Randomized,Open Label,Controlled Study.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 178
- 试验地点
- 10
- 主要终点
- survival of all randomized patients at month 24 (favorable event). Mortality by month 24 and withdrawal from the study will be considered to be unfavorable events.
研究概览
简要总结
Background
Hepatic intra-arterial chemoembolization (TACE) is proposed when potentially curative therapy (eg. surgical resection, percutaneous ablation)is no longer possible. Prospective and non-randomized retrospective studies showed TACE to be capable to increase survival vs controls. In 2002 the first results of two RCTs were published which had been conducted on unresectable HCC patients, designed to assess the impact produced by TACE on survival, demonstrated a statistically significant advantage in TACE treated patients compared to controls. The same results have been confirmed by a meta-analysis conducted on 14 trials published in literature. The limitations of TACE are represented however by the difficulties in obtaining a complete necrosis of the lesion treated and for this reason new embolization agents are being developed to increase the efficacy of TACE in HCC as the microsphere, in poly vinyl alcohol and co-acrylic acid that are not reabsorbable and induce permanent embolization. The first experimental studies using microsphere showed the good tolerability and the higher rate of tumor necrosis, but no RCTs have been conducted to investigate their impact on survival. Objectives. The primary aim of this study is to compare 2 years survival of patients randomized to selective traditional TACE or selective TACE via microspheres loaded with Doxorubicin. Secondary objectives investigate the time to progression of disease (radiologic and symptomatic) by radiologic, laboratory tests and the QoL questionnaire administration. Methods. This is a multicentre, randomized, open-label, active controlled study in HCC patients treated with standard TACE vs TACE with doxorubicin - loaded microsphere. The study comprises a selection period, a treatment period and a follow up phase with a total duration of 2 years from randomization. Expected results. The sample size(alfa 5%, power 80%) is adequate to detect a 20% difference between TACE with microsphere vs traditional TACE.
详细描述
INTRODUCTION
Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in man. Liver transplantation, surgical resection and percutaneous ablation (alcoholization and thermal ablation) are curative therapies and can be used only in patients presenting with early phase disease, whereas 50-70% of HCC diagnoses are made when the disease has already reached the intermediate-advanced phase.
For HCC for which potentially curative therapy is no longer possible, palliative treatment has been proposed by hepatic intra-arterial chemoembolization (TACE) consisting of an infusion of cisplatin or doxorubicin emulsified with lipiodol, followed by a transient flow blockage achieved by reabsorbable particles (gelatin sponge particles). The rationale for the intra-arterial administration of chemotherapy agents in association with embolization material lies in the presence of double hepatic vascularization: hepatocytes are mainly vascularized by the portal structure (approximately 90%) whereas malignant cells are vascularized by the arterial structure (approximately 90%).
Prospective and non-randomized retrospective studies showed TACE to be capable of increasing survival (60-88% at one year, 30-60% at 2 years and 18-50% at 3 years) versus controls.
Despite these encouraging results, none of the first six RCT studies investigating TACE showed a significant increase of survival but only a decrease in tumor dimension. These trials however included mainly large tumors, in patients with severe liver disease, and these conditions may well have masked the benefits offered by TACE.
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
- •Diagnosis of HCC: based on the Guidelines issued by AASLD (American Association for the Study of Liver Diseases) (latest diagnostic radiological imaging performed within 1 month from enrolment)
- •HCC for which transplantation, surgical resection or percutaneous ablation are not indicated
- •Absence of extrahepatic cancer involvement
- •Absence of portal vein thrombosis, with the exception of thrombosis of a segment branch of the portal vein
- •Child-Pugh class A or B
- •Performance status: ECOG 0-2 (WHO)
- •Target liver lesion measurable as per WHO modified EASL criteria
- •Life expectancy of at least 3 months in absence of treatments.
- •Prior surgical or locoregional ablation or TACE treatments are allowed for lesions other than the target lesion treated and monitored to define tumor response.
- •The following laboratory parameters must be met:
- •Creatinine ≤ 1.50 mg/dL, Bilirubin ≤ 2.5 mg/dL, Albumin >= 30 g/L White blood cells >= 1.5 x 109/L, PLT >= 50 x 109/L, PT >= 50%
- •Signature of informed consent obtained.
排除标准
- •Infiltrative HCC
- •Liver tumor is undefined, unmeasurable or not assessable
- •Occlusive thrombosis of the common portal trunk or of a main branch (right or left).
- •Ascites, F3-type varices.
- •Contraindications to arteriography
- •Hepatofugal portal flow
- •Presence of hemodynamically relevant abnormalities of hepatic arterial structure, such as not to allow for a correct and safe delivery of microspheres.
- •Prior TACE to the target lesions
- •Presence of chronic or acute co-morbidities (to lungs, heart, kidneys or brain) because of which the patient is not eligible to receive the treatment foreseen by the protocol.
- •Prior neoplasias in the 5 preceding years or concomitance of other neoplasias at enrolment, wtih the exception of cutaneous basal cell or squamous cells carcinoma or carcinoma in situ of the uterine cervix
- •Presence of localized or systemic infections (with the exception of HIV infecton responsive to therapy).
- •Pregnant women (women of child-bearing potential will have a pregnancy test done) and breastfeeding women;
- •Known or suspect hypersensitivity to the investigational drug or to the investigational pharmacological class;
- •Patients presenting with severe clinical conditions which in the opinion of the investigator contraindicate patient participation in the study;
- •Use of investigational drugs in the last month prior to inclusion into the study
- •Patients who are not capable of complying with the procedures established by the protocol and of signing the informed consent. In case of minors or incapacitated patients unable to release their informed consent to take part in the study, the consent must be released and signed also by the parents/guardian or by the legal representative. Minors or incapacitated patients must as well sign the informed consent to the best of their ability.
结局指标
主要结局
survival of all randomized patients at month 24 (favorable event). Mortality by month 24 and withdrawal from the study will be considered to be unfavorable events.
时间窗: From first TACE treatment to month 24
次要结局
- Radiological tumor response; TTSP; TTP; Overall duration of response; Quality of life; ECOG score; Impact on liver function; No.of treatments administered.(From first TACE to month 24)
研究者
Rita Golfieri
MD
University of Bologna