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

Yale University

Status: Completed

Conditions: Liver Cancer

Treatments: Device: Drug-eluting beads loaded with doxorubicin hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00293397

CDR0000456493

HOC-05042805

P30CA006973 (U.S. NIH Grant/Contract)

JHOC-J0516

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Drug-eluting bead transarterial chemoembolization (DEB-TACE)

Experimental group

Description:

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.

Treatment:

Device: Drug-eluting beads loaded with doxorubicin hydrochloride