Irinotecan Loaded Drug-eluting Beads (DEBIRI) for the Treatment of Liver Metastases From Colorectal Cancer - An Observational Study and Patient Registry
试验速览
- 阶段
- 不适用
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Time to Hepatic Progression (TtHP)
研究概览
简要总结
Purpose:
The purpose of this study is: to assess and define the current practice of the delivery of irinotecan loaded drug eluting beads in the treatment of liver metastases from colorectal cancer; to correlate how the delivery of this drug compares to worldwide/European guidelines, and to determine which individual variations in delivery may be associated with an increased complication profile or better outcome.
The aim of the study is to:
- Prospectively evaluate the number of centres providing DEBIRI
- To determine the number of patients being treated nationally per year
- To evaluate individual variations in practice with respect to number of treatments, method of pain control, side effect profile, and complication profile.
- To collect patient specific data subsets to allow correlation and causal associations between these individual variations, and relate these to efficacy and survival during the study period.
详细描述
The study is to evaluate and audit the use of drug eluting beads loaded with irinotecan chemotherapy for the treatment of colorectal liver metastases. Colorectal cancer (CRC) is the third most common malignancy in men and the second in women, affecting more than 1.2 million people per year worldwide.
The development of metastases is the main cause of death in patients with CRC. Surgical resection is the first-line treatment for hepatic CRC metastases.
Unfortunately, despite the progress of modern surgical techniques, radical resection is possible only in l0%-25% of patients with CRC metastases confined to the liver.
Studies have suggested that DEB-IRI TACE may offer a novel approach to locoregional hepatic chemotherapy. DEB-IRI TACE allows a dose of irinotecan chemotherapy to be delivered directly into the liver, and thus has a significantly reduced side effect profile in comparison to systemic chemotherapy. It can be given alongside a reduced dose of systemic therapy or in some cases can be given instead of systemic therapies.
Pharmacokinetic analyses have shown the bioavailability from DC Bead (Biocompatibles UK, Farnham, United Kingdom)- based delivery of irinotecan is double that of intravenous infusion, attributable to reduced drug clearance for the former. Experimental animal studies have confirmed that DEB-IRI TACE induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis compared with intraarterial or intravenous injection of irinotecan. Pilot clinical trials have suggested that DEB-IRI TACE administered in combination with systemic 5-fluorouracil and oxaliplatin in chemotherapy-naive patients or as a stand-alone regimen in patients with disease refractory to multiple lines of intravenous chemotherapy- may result in high rates of tumor response. In a randomized controlled study, DEB-IRI TACE showed a significant overall survival benefit with respect to a systemic regimen including irinotecan, 5-fluorouracil, and leucovorin in a series of 74 patients who had received at least two or three lines of chemotherapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any race or sex
- •Histological diagnosis of Colorectal malignancy.
- •Histological or radiological evidence of liver metastases from Colorectal Primary.
- •Not suitable for surgical resection or ablation with curative intent.
- •Metastatic liver burden occupying less than 50% of liver volume
- •Liver dominant disease (defined as 80% or more of the overall whole body tumour burden confined to the liver).
- •At least 1 measurable liver metastasis measuring over 1cm in size (RECIST 1.1 criteria to be applied).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •ECOG 2 may occasionally be permissible on an individual patient by patient basis in line with local guidelines.
- •Life expectancy 3+ months.
- •Lack of pregnancy with ongoing use of acceptable contraceptive(in premenopausal women.
- •Patent main portal vein.
- •Adequate haematologic function as evidenced by: Haemoglobin of at least 8g/dl, platelets of at least 50 x 109/l, and International Normalised Ratio (INR) of under 1.
- •Adequate liver function as evidence by a bilirubin level of less than twice the upper limit of normal.
- •Deemed to be a suitable patient for DEBIRI treatment by MDT consensus.
- •Consenting to inclusion in registry.
排除标准
- •Any patient not fitting inclusion criteria.
- •Previous or concurrent non-colorectal malignancy.
- •No contraindication to Irinotecan administration.
- •Uncorrectable clotting abnormality
- •Documented allergy to contrast media that cannot be managed with standard care(steroids and antihistamines)
- •Family, psychological, social or geographical circumstances preventing the patient from undergoing follow-up or from complying with protocol procedures
结局指标
主要结局
Time to Hepatic Progression (TtHP)
时间窗: 2 years after treatment
Progression as measured by RECIST 1.1 criteria up to 2 years after treatment
次要结局
- Overall survival (OS)(2 years after treatment)
- Adverse events(4 months after treatment)
- Quality of Life post DEBIRI delivery(4 months after treatment)
研究者
Damian Mullan
Consultant Radiologist
The Christie NHS Foundation Trust