Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity (ELDORADO)

University of Magdeburg

Status and phase

Completed

Phase 2

Conditions

Radiation Induced Liver Disease

Irradiation Damage

Liver Metastases

Colorectal Cancer

Treatments

Drug: Enoxaparin

Drug: Pentoxifylline

Drug: Ursodeoxycholic Acid

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01149304

RAD052

2008-002985-70 (EudraCT Number)

MD-R20080507 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

22 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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)