Evaluation of the Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity After Brachytherapy of Liver Metastases From Colorectal Carcinoma, Assessed in a Prospective Randomised Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- HDR-brachytherapy isodose (measured in Gy) that corresponds to the metastases without enhancement of Gd-EOB-DTPA in MR imaging using an axial T1 THRIVE sequence.
研究概览
简要总结
To evaluate whether a combination regimen of pentoxifylline, ursodeoxycholic acid and enoxaparin provides a protective effect on the liver parenchyma after high dose rate (HDR) brachytherapy.
详细描述
A preventive effect of pentoxifylline, ursodeoxycholic acid and low dose low molecular weight heparin on pathological processes in healthy tissue after irradiation is described in clinical studies on percutaneous liver irradiation and on bone marrow transplantation. However, data remains inconclusive.
This exploratory study aims at assessing whether a protective effect of the combination of pentoxifylline, ursodeoxycholic acid and enoxaparin can be demonstrated in a limited number of patients with liver metastases of colorectal cancer after HDR brachytherapy.
All patients receive a single fraction CT/MRI-guided HDR-brachytherapy of colorectal liver metastases using Iridium-192 as a standard therapy. The follow-up consists of 4 MRI controls of the abdomen using the hepatocyte-specific contrast agent Gd-EOB-DTPA (Primovist) after 3 days, 6 weeks, 3 months and 6 months as well as blood samples and a questionnaire taken the same time.Within the study, 22 patients are given low dose low molecular weight heparin, pentoxifylline and ursodeoxycholic acid for 8 weeks starting with the preinterventional day. Another 22 patient will receive the standard therapy without the medication. After completion of the follow-up, MRI volume data of the lesion will be acquired and compared to the dosimetric treatment plan. Blood samples are tested for liver-specific and inflammatory laboratory parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Age 18 to 80
- •If female, postmenopausal or surgically sterilized
- •Liver metastases from colorectal carcinoma scheduled for a CT/MRI-guided single-fraction interstitial HDR brachytherapy
- •Non-cirrhotic liver
- •Life expectancy longer than 6 months
- •willing and able to undergo all study procedures
- •Having voluntarily provided written and fully informed consent
排除标准
- •Women who are pregnant, lactating or who are of childbearing potential
- •Liver cirrhosis
- •Hepatitis B
- •Hepatitis C
- •Patients being clinically unstable
- •Uncooperative, in the investigator's opinion
- •Having been previously enrolled in this study
- •Participating in another therapy-modulating clinical trial
- •Contraindication for MRI
- •Contraindication or hypersensitivity to one or more components of Gd-EOB-DTPA, Enoxaparin, Ursodeoxycholic acid and/or Pentoxifylline
- •Any prior irradiation therapy of the liver
- •Close affiliation with the investigational site; e.g. a close relative of the investigator
- •Severe coronary artery disease
- •Autoimmune diseases
- •Acute bacterial endocarditis
- •Active major bleedings and high rish of uncontrolled haemorrhage
- •Patients with severe or moderate renal impairment (GFR below 60 mL/min/1.73 m2 according to the MDRD or Cockroft-Gault formula, calculated from a creatinine value obtained within 1 week before each planned Primovist-enhanced MR examination)
研究组 & 干预措施
Group A
Medication group with patients receiving the study medication according to the study protocol for 8 weeks after HDR brachytherapy.
干预措施: Pentoxifylline (Drug)
Group A
Medication group with patients receiving the study medication according to the study protocol for 8 weeks after HDR brachytherapy.
干预措施: Ursodeoxycholic Acid (Drug)
Group A
Medication group with patients receiving the study medication according to the study protocol for 8 weeks after HDR brachytherapy.
干预措施: Enoxaparin (Drug)
结局指标
主要结局
HDR-brachytherapy isodose (measured in Gy) that corresponds to the metastases without enhancement of Gd-EOB-DTPA in MR imaging using an axial T1 THRIVE sequence.
时间窗: One day prior to brachytherapy.
The primary variable is the HDR-brachytherapy isodose that encloses liver tissue with a diminished uptake of the hepatocyte selective contrast agent GD-EOB-DTPA. By identifying the damaged volume in every layer of the axial T1 THRIVE image, 3D data can be calculated and correlated to a specific isodose when merged with the 3D irradiation treatment plan. Prior to brachytherapy, the baseline volume of the metastases will be measured instead of the liver tissue damaged by irradiation.
HDR-brachytherapy isodose (measured in Gy) that corresponds to the irradiated liver tissue without enhancement of Gd-EOB-DTPA in MR imaging using an axial T1 THRIVE sequence.
时间窗: 6 months after brachytherapy.
The primary variable is the HDR-brachytherapy isodose that encloses liver tissue with a diminished uptake of the hepatocyte selective contrast agent GD-EOB-DTPA. Liver tissue without enhancement of Gd-EOB-DTPA around the irradiated metastases is defined as damage by irradiation. By identifying the irreversibly damaged volume in every layer of the axial T1 THRIVE image, 3D data can be calculated and correlated to a specific isodose when merged with the 3D irradiation treatment plan. Imaging up to 3 months after brachytherapy is mandatory for inclusion in the analysis.
次要结局
- Correlation between the HDR brachytherapy isodose that corresponds to damaged live tissue as defined by missing Gd-EOB-DTPA enhancement in MR imaging and liver-specific laboratory values.(One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.)
- Quality of live.(One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.)
- Safety of the study drugs.(Up to 6 months after brachytherapy.)
研究者
Robert Damm
Dr. med. Robert Damm
University of Magdeburg