Feasibility and Prospective Randomized Study of Transarterial Chemoembolization Using Irinotecan Bead in Combination With Second Line Chemotherapy in the Treatment of Patients With Unresectable Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 3
- 主要终点
- Progression Free Survival
研究概览
简要总结
The primary objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in combination with intravenous chemotherapy versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer. The results of this study are intended to be used in support of a PMA application for a combination device
详细描述
There are many treatments for metastatic colorectal cancer to the liver, and both the application and outcomes are highly dependant on the patients disposition. Whilst resection results in the best long term survival, it is often not a viable treatment option.
Irinotecan Bead is an embolization device intended to treat colorectal cancer metastases of the liver. As an adjunct to this, irinotecan is present in the microspheres which is released in a controlled manner into the local environment of the tumor. Irinotecan Bead is a combination of an approved embolization device and an approved chemotherapy agent. The device is a PVA based embolization agent from Biocompatibles UK Ltd, and the irinotecan is sourced from an FDA approved supplier.
Irinotecan, a topoisomerase inhibitor, was the first systemic chemotherapy drug other than 5-Fluorouracil (5-FU) to demonstrate significant activity in the treatment of metastatic colorectal cancer. Irinotecan is approved for use in combination with 5-FU/folinic acid in patients without prior chemotherapy, and for the second-line treatment of metastatic colorectal cancer as a single agent in patients who have failed an established 5-FU containing treatment regimen.
The purpose of this combination device as a treatment for cancer in the liver is twofold:
(i) Nutrient and oxygen starvation of the tumor. (ii) Minimization of chemotherapy wash-out with prolonged contact with tumor tissue.
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
- •Patients with confirmed diagnosis of stage IV colorectal cancer with unresectable liver metastases (primary tumor may be present)
- •Patients with at least one measurable liver metastases, with size > 1cm (RECIST criteria)
- •Patients with liver dominant disease defined as ≥50% tumor body burden confined to the liver
- •Patients with patent main portal vein
- •Performance status ≤ 2 ECOG
- •Life expectancy > 6 months
- •Aged ≥18 years
- •Patient has failed (discontinued for progression or toxicity) one prior line of chemotherapy for metastatic disease, preferably oxaliplatin-based (e.g. FOLFOX, CAPOX). Note that substitutions of oral versus IV 5-FU formulations, changes in 5-FU schedules, or discontinuations/re-starting of the same chemotherapy drugs will not be considered as separate lines of therapy, nor will the addition of "biologics" such as bevacizumab, cetuximab, or panitumumab
- •Patient has no previous treatment with irinotecan
- •At least 4 weeks since last administration of last chemotherapy and /or radiotherapy
- •Hematologic function: ANC ≥ 1.5 x 109/L, platelets ≥75 x10-9/L, INR <1.5 (patients on therapeutic anticoagulants are not eligible)
- •Adequate liver function as measured by: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl,
- •Adequate renal function (creatinine ≤ 2.0mg/dl)
- •Women of child bearing potential and fertile men are required to use effective contraception (negative serum βHCG/urine test for women of child-bearing age)
- •Signed, written informed consent
排除标准
- •Patient eligible for curative treatment (i.e. resection or radiofrequency ablation). Note: resectability is defined as a single tumor <5cm with adequate liver function defined: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl
- •Contraindications to irinotecan:
- •Chronic inflammatory bowel disease and/or bowel obstruction
- •History of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate, lactic acid or to any of the excipients of Camptosar
- •Severe bone marrow failure
- •History of Gilbert Syndrome (specific testing not required)
- •Concomitant use with St John's Wort (Hypericum)
- •Active bacterial, viral or fungal infection within 72 hours of study entry
- •Women who are pregnant or breast feeding
- •Previous irinotecan based therapy for metastatic disease
- •Patients' whose only measurable disease is within an area of the liver previously subject to radiotherapy
- •Allergy to contrast media that cannot be managed with standard care (e.g. steroids)
- •Presence of another malignancy with the exception of cervical carcinoma in situ and stage I basal or squamous carcinoma of the skin
- •Contraindicated for MRI or CT
- •Patients previously treated with transarterial embolization (with or without chemotherapy)
- •Any contraindication for hepatic embolization procedures:
- •Large shunt as determined by the investigator (pretesting with TcMMA not required)
- •Severe atheromatosis
- •Hepatofugal blood flow
- •Main portal vein occlusion (e.g. thrombus or tumor)
- •Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk, that would preclude the safe use of chemoembolization or would interfere with study participation
研究组 & 干预措施
Chemoembolization
Chemoembolization with Irinotecan Bead in combination with Intravenous Chemotherapy Group (test arm)
干预措施: Chemoembolization with irinotecan Bead (Procedure)
Chemoembolization
Chemoembolization with Irinotecan Bead in combination with Intravenous Chemotherapy Group (test arm)
干预措施: Irinotecan (Drug)
Chemotherapy
Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
干预措施: Irinotecan (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: 1 year
次要结局
- Local Tumor Response (Extent of Necrosis in the Treated Lesions)(1 year)
- Toxicity, Adverse Events and Serious Adverse Events (NCI CTCAE v3.0)(6 weeks)
- Tumor Response (RECIST)(1 year)
- Change in Tumor Marker(1 year)
- Performance Status (ECOG)(1 year)
- Hepatic Progression Free Survival(1 year)
- Overall Survival(1 year)