Safety and Efficacy of Doxorubicin-eluting-bead Embolization in Patients With Advanced Hepatocellular Carcinoma

January 15, 2018 updated by: Yoon Jun Kim, Seoul National University Hospital

Phase4, to Assess Time to Progression (TTP) and Safety Profile of Doxorubicin-Eluting-Bead Embolization(DEBDOX) in Patients With Advanced HCC

Safety and efficacy of doxorubicin-eluting-bead embolization in patients with advanced hepatocellular carcinoma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Transarterial chemoembolization (TACE) represents a first-line non-curative therapy for hepatocellular carcinoma (HCC). TACE is associated with unsatisfactory long-term outcomes. The objective response rate of TACE is only 15% to 55%, and the tumor recurrence rate is 70% at 5 years. One potential reason for this may be the increase in plasma vascular endothelial growth factor (VEGF) levels after TACE. Disturbances in the tumor microenvironment following TACE result in increased hypoxia, leading to an up-regulation in hypoxia inducible factor-1a, which in turn up-regulates VEGF and platelet-derived growth factor receptor (PDGFR) and increases tumor angiogenesis. TACE is considered for the patients with unresectable HCCs that are also ineligible for local ablative therapy. The lack of portal blood flow (because of portal vein thrombosis, portosystemic anastomoses or hepatofugal flow) had been considered as the main contraindication of TACE. However, it has been reported that TACE can be safely performed in a selected population of patients with main portal vein invasion, if they have well-preserved liver function due to collateral blood supply.

DC Beads are a novel drug delivery embolization system comprised of biocompatible, non-resorbable polyvinyl alcohol polymer hydrogel beads which can be loaded with cytotoxic drugs. The beads have a high affinity for drugs and this enables the gradual release of doxorubicin into the tumor, allowing a longer intratumoral exposure and less systemic exposure of the drug, reducing systemic toxicity. One multivariate analysis study showed that the median survival duration for the patients with portal vein invasion who were treated with DC-bead TACE (DEBDOX) were 176 days, retrospectively.

In international, multicenter, randomized phase II trial, the drug-eluting bead group showed higher rates of complete response and objective response compared with the cTACE group (27% vs. 22%, 52% vs. 44% respectively). The hypothesis of superiority was not met. However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response compared to cTACE.

Here, the investigators will investigate the safety and efficacy of DC Bead TACE in patients with advanced HCC with portal vein invasion.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:[Stage C HCC according to the BarcelonaClinic of Liver Cancer]

  1. Signed written informed consent.
  2. Clinical or histological diagnosis of HCC based on the guidelines of the American Association for the Study of Liver Diseases.
  3. At least one typical enhanced lesion that is bi-dimensionally measurable by multiphasic spiral CT scan or dynamic contrast-enhanced MRI.
  4. Tumor conditions confirmed by abdominal imaging (contrast enhanced CT ± MRI) performed within 1 month prior to the enrollment:
  5. Age of at least 18 years and less than 80 years.
  6. ECOG Performance Status of 0 or 1.
  7. Child-Pugh class A or B (Child-Pugh score ≤ 7).
  8. Life expectancy of at least 16 weeks.

  9. Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements (no transfusion, no restoration), conducted within 14 days prior to screening:

    • Hemoglobin ≥ 8.0 g/dL
    • Absolute neutrophil count ≥ 1,000/mm3
    • Platelet count ≥ 50,000/μL
    • Total bilirubin <2.5 mg/dL
    • Serum albumin ≥2.8 g/dL
    • ALT and AST < 5 × upper limit of normal
    • PT-INR ≤ 2.3 or Prothrombin Time-sec ≤ 6 sec
    • Serum creatinine ≤ 1.7 mg/dL

Exclusion Criteria:

  1. A history of receiving any systemic therapy of the molecularly targeted agents, immunotherapy or cytotoxic chemotherapy for the treatment of HCC
  2. Invasion of inferior vena cava (Vv3), or invasion of first order branch of the biliary duct (B3)
  3. History or presence of hepatic encephalopathy
  4. Ascites, moderate, large or intractable
  5. Active clinically serious infections (> grade 2, NCI-CTC version 4.0), including spontaneous bacterial peritonitis.
  6. Untreated active chronic hepatitis B
  7. Esophageal or gastric varices≥ F2 (grade 2) with red color sign positive without prophylaxis (non-selective beta-blocker or endoscopic variceal ligation) or history of variceal bleeding without endoscopic variceal ligation/ injection sclerosis
  8. Active ulcer of stomach or duodenum: untreated or presence of visible vessel
  9. Any major surgery within 4 weeks, or any minor surgery within 2 weeks prior to signing the informed consent form
  10. Candidate for liver transplant and a history of liver transplantation
  11. History of cardiac disease: congestive heart failure greater than NYHA class 2; active coronary artery disease; cardiac arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension and diabetes mellitus
  12. History of AIDS/HIV infection.
  13. Seizure disorder requiring medication.
  14. History of organ allograft.
  15. Evidence or history of bleeding diathesis, or thromboembolic events requiring treatment
  16. Current renal dialysis.
  17. Previous or concurrent cancer that has a primary site or histology distinct from HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis, and T1] or any cancer curatively treated less than 3 years prior to enrollment.
  18. History of alcohol abuse (male > 210g/week, female >140g/week)
  19. Any contraindication for chemoembolization except major branch of portal vein invasion
  20. Any contraindication for doxorubicin administration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Doxorubicin loadeing-DC Bead(Device)

DC Bead comprises hydrogel microspheres that are biocompatible, hydrophilic, non resorbable, precisely calibrated and capable of loading doxorubicin.

DC Bead is produced from polyvinyl alcohol.
Procedure: Device(DC Bead)
Doxorubicin-Eluting-Bead Embolization (DEBDOX), DC Bead are a novel drug delivery embolization system

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of Time to progression of hepatocellular carcinoma 30 patients.
Time Frame: up to at least 3 years
The rate of Time to progression of doxorubicin eluting bead embolization in patients with advanced hepatocellular carcinoma.After the treatment period, patients will undergo follow up for safety within 30 days (+7 days) of final DEBDOX, and will undergo follow up for survival every 84 days (±14 days) (84 days is the day counted from the DEBDOX TACE) for at least 3 years.
up to at least 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Collaborators

BTG International Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Actual)

November 1, 2017

Study Completion (Anticipated)

August 1, 2018

Study Registration Dates

First Submitted

July 29, 2015

First Submitted That Met QC Criteria

August 14, 2015

First Posted (Estimate)

August 17, 2015

Study Record Updates

Last Update Posted (Actual)

January 17, 2018

Last Update Submitted That Met QC Criteria

January 15, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DCbead_PVTT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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