Clinical trial NCT01259024: The LC Bead Trial; Transarterial Chemoembolization of Hepatocellular Carcinoma (HCC)With a Drug-eluting Bead
Official title: Hepatic Arterial Embolization of Hepatocellular Carcinoma With a Doxorubicin Eluting Bead
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
chemoembolization
transarterial chemoembolization
liver cancer
doxorubicin
drug-eluting beads
LC Bead
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2010-12-13
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: To Collect Data on Patients With Hepatocellular Carcinoma (HCC) Being Treated With Chemoembolization With Doxorubicin Eluting Beads (DEB).
timeFrame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
measure: 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.
timeFrame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
measure: Monitor Safety After Treatment of DEB by Measuring Liver Function Tests and Assessing Performance Status.
timeFrame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Secondary outcomes:
measure: To Track Survival Following Treatment With DEB to Confirm That Any Gains in Response Are Associated With an Increase in Survival.
timeFrame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital/Washington Univesity School of Medicine
state: Missouri
Study officials:
affiliation: Mallinckrodt Institute of Radiology/Washington University School of Medicine
name: Nael E. Saad, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Biselli M, Andreone P, Gramenzi A, Trevisani F, Cursaro C, Rossi C, Ricca Rosellini S, Camma 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. doi: 10.1016/s1542-3565(05)00425-8.
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.
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.