The LC Bead Trial; Transarterial Chemoembolization of Hepatocellular Carcinoma (HCC)With a Drug-eluting Bead

Hepatocellular Carcinoma Clinical Trial

Official title:

Hepatic Arterial Embolization of Hepatocellular Carcinoma With a Doxorubicin Eluting Bead

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01259024
• Other study ID #: 201108256
• Status: Terminated
• Phase: N/A
• Start date: December 2011
• Est. completion date: April 2012

Study information

• Verified date: April 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study involves the combined use of the FDA approved device, LC Bead and the FDA approved drug, Doxorubicin for the treatment of primary hepatocellular carcinoma (HCC). The current indication of the LC Bead is for the embolization of hypervascular tumors and arteriovenous malformations. The study is designed to establish if drug eluting beads are more effective and less toxic than standard chemoembolization treatment.

Description:

Patients will be given IV fluids and premedication with 500 mg metronidazole, 10 mg dexamethasone, and 8 mg ondansetron to prevent infection, limit pain and nausea. The femoral artery will be accessed and a catheter advanced into the superior mesenteric artery. Positioning of all catheters will be confirmed by injection of radiographic contrast material. Superior mesenteric angiography will be performed with images obtained through the portal venous phase to confirm patency and flow direction of the portal vein and determine the presence of aberrant supply to the right lobe of the liver by the superior mesenteric artery. The catheter will then be advanced into the celiac artery. Celiac angiography will be performed to determine remainder of the hepatic arterial anatomy. Selection of the tumor bearing artery will then be performed with a microcatheter which is advanced through the catheter in the celiac artery origin. Selection will be guided by fluoroscopy and will be at the lobar level or peripherally in all cases. Once the feeding vessel has been selected and confirmed by contrast injection, the physician will initiate embolization with LC Beads. Up to two vials of LC Beads will be administered. One 2 mL vial each of 300-500 and 500-700 um LC Beads with 37.5 mg/mL doxorubicin will be prepared. The LC Beads will be mixed with radiographic contrast to ensure fluoroscopic visibility during injection. Under careful fluoroscopic control, the vial of 300-500 um vial will be infused, followed by the vial of 500-700 um LC Beads. If the artery reaches stasis prior to administration of both vials, the residual volume of LC Beads will be noted on the surgical report form. If after administration of the DEB, there is residual antegrade flow in the feeding artery, it will be treated with bland embolization similar to chemoembolization. After confirming that the artery is appropriately treated, all catheters and guidewires will be removed from the femoral artery and hemostasis obtained.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18

• Patent main portal vein with hepatopetal flow

• Bilirubin less than or equal to 2.5 mg/dl, albumin >2.8g/dl, alkaline phosphatase <630IU/L, AST <235IU/L, ALT <265IU/L, INR <2.0, PTT <40sec., absolute neutrophil count >1K/cumm, platelet count >100K/cumm

• No encephalopathy

• No previous biliary ductal intervention

• Child A status

• Confirmation of Hepatocellular Carcinoma (through biopsy or radiological exam)

• Unresectable HCC and ineligible for possible curative therapies

• Normal ECG with QT <480 msec within the previous 2 months

• Normal MUGA scan within the previous 2 months

• Measureable disease per the Response Evaluation Criteria in Solid Tumors (RECIST)

• Subject is competent and willing to provide written informed consent in order to participate in the study

Exclusion Criteria:

• Thrombosis or hepatofugal flow in the main portal vein; presence of a large shunt which in the operator's opinion precludes embolization

• Replacement of greater than 50% of the liver parenchyma by tumor

• Bilirubin greater than or equal to 2.6 mg/dl

• ECOG performance status of 2 or greater

• Previous liver directed therapy

• Previous biliary intervention (excluding cholecystectomy)

• Allergy to iodinated contrast used for angiography

• Elevated creatinine greater than or equal to 1.8 mg/dl

• Women who are pregnant or nursing

• Patients in which any of the following are contraindicated: 1)the use of doxorubicin, 2)MRI or CT scans, 3) Hepatic embolization procedures

• Patients with active bacterial or fungal infection that is deemed to be clinically significant by the investigator

• Patients with cardiac disease, including congestive heart failure, recent myocardial infarction, or uncontrolled arrhythmias

• Non-English speaking patients

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Device:
• transarterial chemoembolization using a drug-eluting bead
Up to 2 vials of LC Beads will be administered. One 2 mL vial each of 300-500 and 500-700 um LC Beads with 37.5 mg/mL doxorubicin will be prepared and mixed with radiographic contrast. Under fluoroscopic control, the vial of 300-500 um vial will be infused, followed by the vial of 500-700 um LC Beads. If the artery does not reach stasis prior to administration of both vials, and there is residual antegrade flow in the feeding artery, it will be treated with bland embolization similar to chemoembolization.

Locations

Country	Name	City	State
United States	Barnes-Jewish Hospital/Washington Univesity School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

Biselli M, Andreone P, Gramenzi A, Trevisani F, Cursaro C, Rossi C, Ricca Rosellini S, Cammà C, Lorenzini S, Stefanini GF, Gasbarrini G, Bernardi M. Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study. Clin Gastroenterol Hepatol. 2005 Sep;3(9):918-25. — View Citation

Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol. 2010 May 1;101(6):476-80. doi: 10.1002/jso.21522. — View Citation

Malagari K, Pomoni M, Kelekis A, Pomoni A, Dourakis S, Spyridopoulos T, Moschouris H, Emmanouil E, Rizos S, Kelekis D. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010 Jun;33(3):541-51. doi: 10.1007/s00270-009-9750-0. Epub 2009 Nov 24. — View Citation

Namur J, Wassef M, Millot JM, Lewis AL, Manfait M, Laurent A. Drug-eluting beads for liver embolization: concentration of doxorubicin in tissue and in beads in a pig model. J Vasc Interv Radiol. 2010 Feb;21(2):259-67. doi: 10.1016/j.jvir.2009.10.026. Erratum in: J Vasc Interv Radiol. 2010 Apr;21(4):596. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Collect Data on Patients With Hepatocellular Carcinoma (HCC) Being Treated With Chemoembolization With Doxorubicin Eluting Beads (DEB).	4-6 weeks after initial treatment, follow-up imaging will be obtained. With positive response to treatment, follow-up imaging will be obtained every 12 weeks. If a new tumor develops or if local progression of the treated malignancy occurs, the patient may be retreated with LC Beads 4-6 weeks after the first treatment with re-imaging 4-6 weeks following each subsequent treatment.	Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Primary	Determine Efficacy (Based on Whether the Study is Positive or Negative) of the Embolization With the LC Bead in Treatment of HCC With Imaging Outcomes Using Modified RECIST and EASL Criteria.	4-6 weeks after initial treatment, follow-up imaging will be obtained. With positive response to treatment, follow-up imaging will be obtained every 12 weeks. If a new tumor develops or if local progression of the treated malignancy occurs, the patient may be retreated with LC Beads 4-6 weeks after the first treatment with re-imaging 4-6 weeks following each subsequent treatment.	Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Primary	Monitor Safety After Treatment of DEB by Measuring Liver Function Tests and Assessing Performance Status.	4-6 weeks after initial treatment, follow-up imaging will be obtained. With positive response to treatment, follow-up imaging will be obtained every 12 weeks. If a new tumor develops or if local progression of the treated malignancy occurs, the patient may be retreated with LC Beads 4-6 weeks after the first treatment with re-imaging 4-6 weeks following each subsequent treatment.	Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Secondary	To Track Survival Following Treatment With DEB to Confirm That Any Gains in Response Are Associated With an Increase in Survival.	4-6 weeks after initial treatment, follow-up imaging will be obtained. With positive response to treatment, follow-up imaging will be obtained every 12 weeks. If a new tumor develops or if local progression of the treated malignancy occurs, the patient may be retreated with LC Beads 4-6 weeks after the first treatment with re-imaging 4-6 weeks following each subsequent treatment.	Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.

External Links

•   Chemoembolization using Drug Eluting Beads is an effective procedure with a favourable pharmacokinetic profile
•   Drug-Eluting Beads Significantly Reduce Doxorubicin Toxicity in Patients With HCC
•   Efficacy of Drug-Eluting Beads in Chemoembolization of Hepatocellular Carcinoma
•   Interventional Radiological Treatment of Hepatocellular Carcinoma