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

NCT01149304 | Completed Phase 2

• 3 other identifiers: RAD0522008-002985-70MD-R20080507
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer; Liver Metastases; Irradiation Damage; Radiation Induced Liver Disease

Keywords

brachytherapy; liver metastases; irradiation; radiation induced liver disease; dosimetry

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  One day prior to brachytherapy.

• 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.

  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 days after brachytherapy.

• 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.

  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.

  6 weeks after brachytherapy.

• 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.

  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.

  3 months after brachytherapy.

• 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.

  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.

  6 months after brachytherapy.

Secondary Outcomes (3)

• 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.

Study Arms (2)

Group A

EXPERIMENTAL

Medication group with patients receiving the study medication according to the study protocol for 8 weeks after HDR brachytherapy.

Drug: Pentoxifylline; Drug: Ursodeoxycholic Acid; Drug: Enoxaparin

Group B

NO INTERVENTION

Comparison group with patients receiving the standard therapy of HDR brachytherapy without the study specific medication.

Interventions

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).

Also known as: Trental (CAS 6493-05-6, ATC C04AD03)

Group A

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).

Also known as: Ursofalk (CAS 128-13-2, ATC A05AA02)

Group A

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.

Also known as: Clexane (CAS 9005-49-6, ATC B01AB05)

Group A

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Magdeburg: lead
• Sirtex Medical: collaborator

Study Sites (1)

Clinic for Radiology and Nuclear Medicine

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Related Publications (1)

• Seidensticker M, Seidensticker R, Damm R, Mohnike K, Pech M, Sangro B, Hass P, Wust P, Kropf S, Gademann G, Ricke J. Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic acid for prevention of radiation-induced liver toxicity. PLoS One. 2014 Nov 13;9(11):e112731. doi: 10.1371/journal.pone.0112731. eCollection 2014.

  PMID: 25393877 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Pentoxifylline; Ursodeoxycholic Acid; Enoxaparin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Jens Ricke, MD

  University of Magdeburg, Faculty for Medicine

• Robert Damm, MD

  University of Magdeburg, Faculty for Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med. Robert Damm

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: June 23, 2010
• Study Start: June 1, 2009
• Primary Completion: November 15, 2017
• Last Updated: November 20, 2017

Record last verified: 2017-11

Locations

DE (1)