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Trial record 15 of 1708 for:    Open Studies | "Radiotherapy"

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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by University of Magdeburg.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Sirtex Medical
Information provided by:
University of Magdeburg
ClinicalTrials.gov Identifier:
NCT01149304
First received: June 4, 2010
Last updated: June 22, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Liver Metastases
Irradiation Damage
Radiation Induced Liver Disease
Drug: Pentoxifylline
Drug: Ursodeoxycholic Acid
Drug: Enoxaparin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official 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

Resource links provided by NLM:


Further study details as provided by University of Magdeburg:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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. [ Time Frame: 3 days after brachytherapy. ] [ Designated as safety issue: No ]

    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.


  • 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. ] [ Designated as safety issue: No ]

    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.


  • 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. ] [ Designated as safety issue: No ]

    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.


  • 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. ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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

  • Quality of live. [ Time Frame: One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy. ] [ Designated as safety issue: No ]
    To evaluate the quality of live comparing both patient groups using the EQ-5D questionnaire and ECOG performance status.

  • Safety of the study drugs. [ Time Frame: Up to 6 months after brachytherapy. ] [ Designated as safety issue: Yes ]
    To assess the safety of the combination regimen of pentoxifylline, low dose low molecular weight heparin, and ursodeoxycholic acid given after HDR brachytherapy.


Estimated Enrollment: 44
Study Start Date: June 2009
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Medication group with patients receiving the study medication according to the study protocol for 8 weeks after HDR brachytherapy.
Drug: Pentoxifylline
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 Name: Trental (CAS 6493-05-6, ATC C04AD03)
Drug: Ursodeoxycholic Acid
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 Name: Ursofalk (CAS 128-13-2, ATC A05AA02)
Drug: Enoxaparin
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 Name: Clexane (CAS 9005-49-6, ATC B01AB05)
No Intervention: Group B
Comparison group with patients receiving the standard therapy of HDR brachytherapy without the study specific medication.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01149304

Contacts
Contact: Max Seidensticker, MD +49(0)391-6713030 max.seidensticker@med.ovgu.de
Contact: Robert Damm +49(0)391-6713030 robert.damm@st.ovgu.de

Locations
Germany
Clinic for Radiology and Nuclear Medicine Recruiting
Magdeburg, Sachsen-Anhalt, Germany, 39120
Sponsors and Collaborators
University of Magdeburg
Sirtex Medical
Investigators
Principal Investigator: Jens Ricke, MD University of Magdeburg, Faculty for Medicine
  More Information

No publications provided

Responsible Party: Prof. Dr. Hermann Josef Rothkötter, Dean, University of Magdeburg, Faculty for Medicine
ClinicalTrials.gov Identifier: NCT01149304     History of Changes
Other Study ID Numbers: RAD052, 2008-002985-70, MD-R20080507
Study First Received: June 4, 2010
Last Updated: June 22, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Magdeburg:
brachytherapy
liver metastases
irradiation
radiation induced liver disease
dosimetry

Additional relevant MeSH terms:
Colorectal Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasm Metastasis
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Rectal Diseases
Pentoxifylline
Ursodeoxycholic Acid
Antioxidants
Cardiovascular Agents
Cholagogues and Choleretics
Enzyme Inhibitors
Free Radical Scavengers
Gastrointestinal Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014