Pilot Study to Assess the Safety and Pharmacokinetics of 70-150μm Drug Eluting Beads Loaded With Irinotecan (DEBIRI) in the Treatment of Hepatic Colorectal Metastases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 4
- 主要终点
- Establish safety and toxicity profile of the irinotecan loaded DEBIRI beads (number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials)
研究概览
简要总结
Background
Hepatic metastases of colorectal cancer (MCC) is quite common and is a major source of morbidity and mortality. There has been evidence to show that hepatic arterial chemoembolisation using DC beads (drug eluting beads, 100-300μm) loaded with irinotecan (DEBIRI) showed improved overall survival when compared to systemic therapy (FOLFIRI), but being larger they have their limitations.
New 70-150μm beads are recently available and currently there is limited data concerning its use. Safety of these beads have not been tested in local patients.
Hypothesis / Aim To study the safety and pharmacokinetics of the smaller 70-150μm DEBIRI in a pilot study of 5 patients. The smaller 70-150μm beads will be able to deliver a more consistent and higher dose to tumoral tissue with a smaller systemic dose. Being smaller and less embolic, it will also be better tolerated. Patients will also be genotyped for their UGT1A1*28 and UGT1A1*6 polymorphism status as the latter genotypes are associated with decreased clearance of irinotecan and SN-38 in Asian patients.
Methods Single centre, pilot study, prospectively recruiting 5 patients with unilobar disease, refractory to systemic chemotherapy
The primary endpoints:
- establish safety and toxicity profile of the irinotecan loaded DEBIRI beads
- establish pharmacokinetics and systemic exposure of irinotecan and its active metabolite, SN-38.
The secondary outcome measurements:
- the incidence and severity of adverse events, liver function parameters and laboratory abnormalities;
- response rate,
- progression free survival
- overall survival
Clinical Significance
This treatment modality has the advantage of directly delivering irinotecan to the liver metastases from colorectal cancer. This local mode of drug delivery may result in a higher intratumoral drug concentration and rapid tumour shrinkage leading to downstaging of the hepatic metastatic lesions. These therapeutic outcomes may also downstage patients to hepatic resection.
详细描述
- Recruitment:
Suitable potential subjects will be identified, namely those who have failed first or second line chemotherapy agents. 2. Liver biopsy Right before the 1st transarterial chemoembolisation procedure, the liver metastases will be biopsied under ultrasound or CT guidance by the IR with a 18G core biopsy needle. Tissue will be sent for histological analysis as well as stored for molecular studies with NCCS. 3. Transarterial chemoembolisation procedure (DEBIRI TACE):
100mg of irinotecan will be loaded into the DEB solution at least 2 hours before the procedure by the pharmacy.
Diagnostic angiography (DSA) will performed under fluoroscopic guidance, most commonly via right groin puncture. Using dedicated catheters, arterial supply of the liver and the tumour involved segments will be determined. A solution of 75-150 μm DEBIRI mixed with non-ionic contrast medium (1:1) will be injected into the artery feeding the metastases.
For unilobar disease, two treatments will be planned, each of them with a maximum of 100mg irinotecan loaded in into the DEB, separated by four weeks. Intravenous fentanyl will be administered for procedural pain relief. Post procedural pain relief medications will be given as deemed necessary by the physician.
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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Metastatic colorectal carcinoma to the liver, both unilobar and bilobar disease
- •Refractory to 1st or 2nd line systemic chemotherapy. Previous chemotherapy had to be discontinued at least 4 weeks prior to study entry
- •Hepatic disease should be 80% or more of total body tumor burden
- •Measurable liver tumour burden was of no more than 60% of the total liver volume.
- •A performance status of 0-2 (WHO criteria).
- •Age <85 years were required.
- •Life expectancy of greater than 3 months
- •Adequate hematologic function (granulocyte count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, INR ≤ 1.3 in patients on anticoagulant therapy)Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal [ULN], AST and ALT ≤ 5 x ULN, and alkaline phosphatases < 5 x ULN) and,
- •Adequate renal function (creatinine clearance > 50 mL/min)
排除标准
- •Extrahepatic tumor burden of > 20%.
- •Patients with unilobar disease who are candidates for surgical resection.
- •Extensive tumor involvement of the liver (>60%)
- •Poor performance status (>2 WHO criteria)
- •Significant diseases of cardiac, renal, bone marrow or pulmonary apparatus, central nervous system involvement, and uncontrolled infection
- •Liver function tests and bilirubin 5-folds more than the normal value
- •History of other cancer except adequately treated in situ carcinoma of the cervix or basal or squamous carcinoma of the skin
- •Absolute neutrophil count of less than 1500 cells/µL
- •Platelet count of less than 100,000/µL
- •Significant portal vein thrombosis
- •Unable to understand nature of study and provide written consent.
结局指标
主要结局
Establish safety and toxicity profile of the irinotecan loaded DEBIRI beads (number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials)
时间窗: 1 year
By looking at the number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials (June 2011)
次要结局
- Tumour response (measured by mRECIST)(6 months)