Clinical trial NCT01149304: Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Liver Metastases
Irradiation Damage
Radiation Induced Liver Disease
Keywords: brachytherapy
liver metastases
irradiation
radiation induced liver disease
dosimetry
Lead sponsor: University of Magdeburg
Sponsor class: OTHER
Collaborators: name: Sirtex Medical
First posted: 2010-06-23
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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 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)

Primary outcomes:
measure: 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.
timeFrame: One day prior to brachytherapy.
measure: 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.
timeFrame: 3 days after brachytherapy.
measure: 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.
timeFrame: 6 weeks after brachytherapy.
measure: 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.
timeFrame: 3 months after brachytherapy.
measure: 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.
timeFrame: 6 months after brachytherapy.
Secondary outcomes:
measure: 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.
timeFrame: One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.
measure: Quality of live.
timeFrame: One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.
measure: Safety of the study drugs.
timeFrame: Up to 6 months after brachytherapy.
Other outcomes:
Locations:
city: Magdeburg
country: Germany
facility: Clinic for Radiology and Nuclear Medicine
state: Sachsen-Anhalt
Study officials:
affiliation: University of Magdeburg, Faculty for Medicine
name: Jens Ricke, MD
affiliation: University of Magdeburg, Faculty for Medicine
name: Robert Damm, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.