Hepatocellular Carcinoma
Conditions
Keywords
hepatocellular carcinoma, chemoembolization, transarterial chemoembolization, liver cancer, doxorubicin, drug-eluting beads, LC Bead
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.
Interventions
DEVICEtransarterial 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.
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Collect Data on Patients With Hepatocellular Carcinoma (HCC) Being Treated With Chemoembolization With Doxorubicin Eluting Beads (DEB). | Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study. | 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. |
| 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. | Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study. | 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. |
| Monitor Safety After Treatment of DEB by Measuring Liver Function Tests and Assessing Performance Status. | Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Track Survival Following Treatment With DEB to Confirm That Any Gains in Response Are Associated With an Increase in Survival. | Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study. | 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. |
Countries
United States
Participant flow
Recruitment details
Participant was screened and recruited on 1/5/2012
Pre-assignment details
Single-arm study - participant received 1st trans-arterial chemoembolization treatment on 1/23/2012, second treatment on 2/20/2012, and third treatment on 3/20/12. Physician decision to withdraw participant on 4/12/2012 due to denial of CMS reimbursement.
Participants by arm
| Arm | Count |
|---|---|
| Doxorubicin-eluting LC Bead transarterial chemoembolization using doxorubicin-eluting LC Beads
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. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Doxorubicin-eluting LC Bead |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
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.
Time frame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Population: 1 patient was enrolled in the study, but was withdrawn by the PI due to inability to obtain CMS reimbursement. The patient was treated off protocol and therefore there are no study results to be analyzed.
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.
Time frame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
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.
Time frame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Population: One participant was enrolled on this IDE and was treated on protocol for 14 weeks. After being made aware that CMS would not provide reimbursement, the PI decided to withdraw the patient and continued to treat off protocol.
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.
Time frame: Patients will participate in protocol until date of death, liver transplantation, or withdrawal from study.
Population: 1 participant was enrolled, analyzed was 0.