Chemoembolization Using Doxorubicin in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

Treatment of Patients With Hepatocellular Carcinoma Using Drug-Eluting Bead Embolization

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor.

PURPOSE: This clinical trial is studying how well chemoembolization using doxorubicin works in treating patients with liver cancer that cannot be removed by surgery.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Device: Drug-eluting beads loaded with doxorubicin hydrochloride

Detailed Description

OBJECTIVES:

• Determine, preliminarily, the feasibility of chemoembolization with GelSpheres™ beads mixed with doxorubicin hydrochloride in patients with unresectable hepatocellular carcinoma.

OUTLINE: This is a pilot study.

Patients undergo catheterization of the hepatic artery followed by chemoembolization comprising an infusion of GelSpheres™ beads mixed with doxorubicin hydrochloride into the target hepatic artery. Patients may receive up to 3 chemoembolization treatments.

After completion of study treatment, patients are followed at 1 month, every 2 months for 1 year, and then every 3 months during year 2.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney kimmel comprehensive cancer center at johns hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of hepatocellular carcinoma (HCC) according to the European Association for the Study of Liver (EASL) disease diagnostic criteria AND the Okuda staging classification

  • No advanced disease, as defined by any of the following:

    • Barcelona Clinic Liver Cancer (BCLC) class C disease, as defined by the following:

      • Vascular invasion, including segmental portal obstruction
      • Extrahepatic spread
      • Cancer-related symptoms (PST of 1-2)

    • BCLC class D disease, as defined by the following:

      • Okuda stage III disease
      • World Health Organization (WHO) performance status 3 or 4
    • Diffuse HCC, defined as massive ill-defined tumor involvement
    • Child-Pugh Class C
• Not eligible for radical therapies (e.g., resection, liver transplantation, or percutaneous therapies)

• No significant liver decompensation

  • Preserved liver function (Child-Pugh class A-B)

    • No ascites (trace ascites allowed)
• No other active primary tumor
• Arteries supplying the lesion must be large enough to accept GelSpheres™ beads

PATIENT CHARACTERISTICS:

• Bilirubin ≤ 3 mg/dL
• Albumin > 2.0 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times the upper limit of normal (ULN)
• No active gastrointestinal bleeding
• No encephalopathy

• No contraindication to hepatic embolization procedures, as indicated by any of the following:

  • Porto-systemic shunt
  • Hepatofugal blood flow
  • Platelet count < 50,000/mm^3
  • International normalized ratio (INR) ≥ 1.8
  • Partial thromboplastin time (PTT) ≥ 39 seconds
  • Renal failure
  • Severe atheromatosis

• No contraindication to doxorubicin hydrochloride administration, as indicated by any of the following:

  • Bilirubin > 5 mg/dL
  • White blood cell (WBC) < 1,500/mm^3
  • Ejection fraction < 50% by isotopic ventriculography or echocardiography
• Not pregnant
• No known allergy to contrast media
• No intolerance to occlusion procedures

• No vascular anatomy or bleeding that would preclude catheter placement or emboli injection, as indicated by any of the following:

  • Active or risk of hemorrhage
  • Patent extra-to-intracranial anastomoses or shunts
  • End arteries leading directly to the cranial nerves
  • Feeding arteries smaller than distal branches from which they emerge
  • Collateral vessel pathways that would potentially endanger normal territories during embolization

PRIOR CONCURRENT THERAPY:

• No prior anticancer therapy for HCC

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Drug-eluting bead transarterial chemoembolization (DEB-TACE); Patients undergo DEB-TACE procedures utilizing LC Beads, polyvinyl alcohol microspheres with diameters of 100-300um or 300-500um, which are loaded with 100mg of doxorubicin hydrochloride and mixed with an equal volume of nonionic contrast media.	Device: Drug-eluting beads loaded with doxorubicin hydrochloride; Doxorubicin eluting beads; Other Names: Gelspheres; LC Beads

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Safety was assessed using the CTCAE v 3.0 criteria, reported are the number of participants that experienced at least 1 event that was grade 2 (moderate) or higher.	1 month
Safety	Safety was assessed using the CTCAE v 3.0 criteria, reported are the number of participants that experienced at least 1 event that was grade 2 (moderate) or higher.	6 months
Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria	Efficacy as assessed by radiographic tumor response using EASL criteria at baseline and at 1 month post-TACE Complete Response (CR): Achieving 100% tumor necrosis of targeted lesions Partial Response (PR): Demonstrating greater than 50% tumor necrosis in targeted lesions Progressive Disease (PD): Reappearance of or increased tumor enhancement greater than 25% in targeted lesions Stable Disease (SD): Not meeting requirements for CR or PR and not demonstrating evidence of progression in targeted lesions.	1 month
Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)	Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, 1 month post treatment. Complete Response (CR): Disappearance of all lesions targeted by therapy Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by therapy Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by therapy Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD.	1 month
Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)	Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, and at 6 months post treatment. Complete Response (CR): Disappearance of all lesions targeted by therapy Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by therapy Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by therapy Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD.	6 months
Efficacy - Overall Survival	Presented are the counts of patients that have survived up to 1 year.	1 Year
Efficacy - Overall Survival	Presented are the counts of patients that have survived up to 2 years.	2 Years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Reyes DK, Vossen JA, Kamel IR, Azad NS, Wahlin TA, Torbenson MS, Choti MA, Geschwind JF. Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J. 2009 Nov-Dec;15(6):526-32. doi: 10.1097/PPO.0b013e3181c5214b.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: February 16, 2006
• First Submitted That Met QC Criteria: February 16, 2006
• First Posted (ESTIMATE): February 17, 2006

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CDR0000456493; P30CA006973 (U.S. NIH Grant/Contract); JHOC-J0516; HOC-05042805