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NCT Number: NCT01149304

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

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.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Irradiation Damage Liver Metastases Neoplasms Neoplasms by Site Radiation Induced Liver Disease Rectal Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinic for Radiology and Nuclear Medicine

Magdeburg, Saxony-Anhalt, 39120, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Pentoxifylline

Drug

Pentoxifylline is given for 8 weeks since the evening of the day of intervention with a dose of 400mg applied three times daily (morning, noon, evening).

Other names: Trental (CAS 6493-05-6, ATC C04AD03)

Ursodeoxycholic acid

Drug

Ursodeoxycholic acid is administered for 8 weeks since the evening of the day of intervention. Dosage is 250mg given three times daily (morning, noon, evening).

Other names: Ursofalk (CAS 128-13-2, ATC A05AA02)

Enoxaparin

Drug

Enoxaparin with a dose of 40mg is injected subcutaneously once a day for 8 weeks since the evening of the day of intervention after the HDR-brachytherapy.

Other names: Clexane (CAS 9005-49-6, ATC B01AB05)

Primary outcomes

  1. 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.

    Time frame: 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.

  2. 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.

    Time frame: 3 days 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 damaged 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.

  3. 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.

    Time frame: 6 weeks 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.

  4. 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.

    Time frame: 3 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.

  5. 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.

    Time frame: 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.

Secondary outcomes

  1. 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.

    Time frame: One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.

    To evaluate the relation between hepatocyte dysfunction by irradiation as assessed in GD-EOB-DTPA-enhanced MRI and changes in liver-specific and inflammatory laboratory values.

    The following laboratory values are included:

    • bilirubin
    • ASAT/ALAT
    • albumin
    • ChE
    • gamma-GT
    • GLDH
    • INR
    • fibrinogen
    • fibrin monomer
    • factor VIII
    • IL 2 + 6
    • PAI
    • protein c + s
    • vWF
    • AT3

  2. Quality of live.

    Time frame: One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.

    To evaluate the quality of live comparing both patient groups using the EQ-5D questionnaire and ECOG performance status.

  3. Safety of the study drugs.

    Time frame: Up to 6 months after brachytherapy.

    To assess the safety of the combination regimen of pentoxifylline, low dose low molecular weight heparin, and ursodeoxycholic acid given after HDR brachytherapy.

Sponsors and collaborators

Lead sponsor

University of Magdeburg

Other

Collaborators

  • Sirtex Medical

Registry information

Official study title

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

Acronym: ELDORADO

Important dates

Study start
2009
Primary completion
2017
First posted
Jun 23, 2010
Registry last updated
Nov 20, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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