Ignite Creation Date:
2025-12-24 @ 7:56 PM
Ignite Modification Date:
2025-12-25 @ 5:31 PM
Study NCT ID:
NCT01149304
Status:
COMPLETED
Last Update Posted:
2017-11-20
First Post:
2010-06-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}], 'ancestors': [{'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D003108', 'term': 'Colonic Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010431', 'term': 'Pentoxifylline'}, {'id': 'D014580', 'term': 'Ursodeoxycholic Acid'}, {'id': 'D017984', 'term': 'Enoxaparin'}], 'ancestors': [{'id': 'D013805', 'term': 'Theobromine'}, {'id': 'D014970', 'term': 'Xanthines'}, {'id': 'D011688', 'term': 'Purinones'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003840', 'term': 'Deoxycholic Acid'}, {'id': 'D002793', 'term': 'Cholic Acids'}, {'id': 'D001647', 'term': 'Bile Acids and Salts'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D002757', 'term': 'Cholanes'}, {'id': 'D006495', 'term': 'Heparin, Low-Molecular-Weight'}, {'id': 'D006493', 'term': 'Heparin'}, {'id': 'D006025', 'term': 'Glycosaminoglycans'}, {'id': 'D011134', 'term': 'Polysaccharides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 22}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-11', 'lastUpdateSubmitDate': '2017-11-16', 'studyFirstSubmitDate': '2010-06-04', 'studyFirstSubmitQcDate': '2010-06-22', 'lastUpdatePostDateStruct': {'date': '2017-11-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2010-06-23', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-11-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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.', 'description': '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.\n\nPrior to brachytherapy, the baseline volume of the metastases will be measured instead of the liver tissue damaged by irradiation.'}, {'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.', 'description': '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.\n\nBy 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.\n\nImaging up to 3 months after brachytherapy is mandatory for inclusion in the analysis.'}, {'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.', 'description': '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.\n\nBy 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.\n\nImaging up to 3 months after brachytherapy is mandatory for inclusion in the analysis.'}, {'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.', 'description': '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.\n\nBy 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.\n\nImaging up to 3 months after brachytherapy is mandatory for inclusion in the analysis.'}, {'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.', 'description': '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.\n\nBy 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.\n\nImaging up to 3 months after brachytherapy is mandatory for inclusion in the analysis.'}], 'secondaryOutcomes': [{'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.', 'description': '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.\n\nThe following laboratory values are included:\n\n* bilirubin\n* ASAT/ALAT\n* albumin\n* ChE\n* gamma-GT\n* GLDH\n* INR\n* fibrinogen\n* fibrin monomer\n* factor VIII\n* IL 2 + 6\n* PAI\n* protein c + s\n* vWF\n* AT3'}, {'measure': 'Quality of live.', 'timeFrame': 'One day prior to brachytherapy, 3 days, 6 weeks, 3 months and 6 months after brachytherapy.', 'description': 'To evaluate the quality of live comparing both patient groups using the EQ-5D questionnaire and ECOG performance status.'}, {'measure': 'Safety of the study drugs.', 'timeFrame': 'Up to 6 months after brachytherapy.', 'description': 'To assess the safety of the combination regimen of pentoxifylline, low dose low molecular weight heparin, and ursodeoxycholic acid given after HDR brachytherapy.'}]}, 'conditionsModule': {'keywords': ['brachytherapy', 'liver metastases', 'irradiation', 'radiation induced liver disease', 'dosimetry'], 'conditions': ['Colorectal Cancer', 'Liver Metastases', 'Irradiation Damage', 'Radiation Induced Liver Disease']}, 'referencesModule': {'references': [{'pmid': '25393877', 'type': 'RESULT', '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThis 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.\n\nAll 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Age 18 to 80\n* If female, postmenopausal or surgically sterilized\n* Liver metastases from colorectal carcinoma scheduled for a CT/MRI-guided single-fraction interstitial HDR brachytherapy\n* Non-cirrhotic liver\n* Life expectancy longer than 6 months\n* willing and able to undergo all study procedures\n* Having voluntarily provided written and fully informed consent\n\nExclusion Criteria:\n\n* Women who are pregnant, lactating or who are of childbearing potential\n* Liver cirrhosis\n* Hepatitis B\n* Hepatitis C\n* Patients being clinically unstable\n* Uncooperative, in the investigator's opinion\n* Having been previously enrolled in this study\n* Participating in another therapy-modulating clinical trial\n* Contraindication for MRI\n* Contraindication or hypersensitivity to one or more components of Gd-EOB-DTPA, Enoxaparin, Ursodeoxycholic acid and/or Pentoxifylline\n* Any prior irradiation therapy of the liver\n* Close affiliation with the investigational site; e.g. a close relative of the investigator\n* Severe coronary artery disease\n* Autoimmune diseases\n* Acute bacterial endocarditis\n* Active major bleedings and high rish of uncontrolled haemorrhage\n* 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)"}, 'identificationModule': {'nctId': 'NCT01149304', 'acronym': 'ELDORADO', 'briefTitle': 'Preventive Effect of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid to Radiation Induced Liver Toxicity', 'organization': {'class': 'OTHER', 'fullName': 'University of Magdeburg'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'RAD052'}, 'secondaryIdInfos': [{'id': '2008-002985-70', 'type': 'EUDRACT_NUMBER'}, {'id': 'MD-R20080507', 'type': 'OTHER', 'domain': "Sponsor's protocol code number"}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group A', 'description': 'Medication group with patients receiving the study medication according to the study protocol for 8 weeks after HDR brachytherapy.', 'interventionNames': ['Drug: Pentoxifylline', 'Drug: Ursodeoxycholic Acid', 'Drug: Enoxaparin']}, {'type': 'NO_INTERVENTION', 'label': 'Group B', 'description': 'Comparison group with patients receiving the standard therapy of HDR brachytherapy without the study specific medication.'}], 'interventions': [{'name': 'Pentoxifylline', 'type': 'DRUG', 'otherNames': ['Trental (CAS 6493-05-6, ATC C04AD03)'], 'description': '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).', 'armGroupLabels': ['Group A']}, {'name': 'Ursodeoxycholic Acid', 'type': 'DRUG', 'otherNames': ['Ursofalk (CAS 128-13-2, ATC A05AA02)'], 'description': '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).', 'armGroupLabels': ['Group A']}, {'name': 'Enoxaparin', 'type': 'DRUG', 'otherNames': ['Clexane (CAS 9005-49-6, ATC B01AB05)'], 'description': '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.', 'armGroupLabels': ['Group A']}]}, 'contactsLocationsModule': {'locations': [{'zip': '39120', 'city': 'Magdeburg', 'state': 'Saxony-Anhalt', 'country': 'Germany', 'facility': 'Clinic for Radiology and Nuclear Medicine', 'geoPoint': {'lat': 52.13129, 'lon': 11.63189}}], 'overallOfficials': [{'name': 'Jens Ricke, MD', 'affiliation': 'University of Magdeburg, Faculty for Medicine'}, {'name': 'Robert Damm, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Magdeburg, Faculty for Medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Magdeburg', 'class': 'OTHER'}, 'collaborators': [{'name': 'Sirtex Medical', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Dr. med. Robert Damm', 'investigatorFullName': 'Robert Damm', 'investigatorAffiliation': 'University of Magdeburg'}}}}