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

NCT ID: NCT01149304

Last Updated: 2017-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Brief Summary

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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

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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.

Conditions

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Colorectal Cancer Liver Metastases Irradiation Damage Radiation Induced Liver Disease

Keywords

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brachytherapy liver metastases irradiation radiation induced liver disease dosimetry

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group A

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

Group Type EXPERIMENTAL

Pentoxifylline

Intervention Type 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).

Ursodeoxycholic Acid

Intervention Type 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).

Enoxaparin

Intervention Type 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.

Group B

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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).

Intervention Type 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).

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Trental (CAS 6493-05-6, ATC C04AD03) Ursofalk (CAS 128-13-2, ATC A05AA02) Clexane (CAS 9005-49-6, ATC B01AB05)

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sirtex Medical

INDUSTRY

Sponsor Role collaborator

University of Magdeburg

OTHER

Sponsor Role lead

Responsible Party

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Robert Damm

Dr. med. Robert Damm

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jens Ricke, MD

Role:

University of Magdeburg, Faculty for Medicine

Robert Damm, MD

Role: PRINCIPAL_INVESTIGATOR

University of Magdeburg, Faculty for Medicine

Locations

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Clinic for Radiology and Nuclear Medicine

Magdeburg, Saxony-Anhalt, Germany

Site Status

Countries

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Germany

References

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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.

Reference Type RESULT
PMID: 25393877 (View on PubMed)

Other Identifiers

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2008-002985-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MD-R20080507

Identifier Type: OTHER

Identifier Source: secondary_id

RAD052

Identifier Type: -

Identifier Source: org_study_id