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

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Drug-eluting beads loaded with doxorubicin hydrochloride

About this trial

This is an interventional treatment trial for Liver Cancer focused on measuring adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Drug-eluting bead transarterial chemoembolization (DEB-TACE)

Arm 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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

Efficacy - Overall Survival

Presented are the counts of patients that have survived up to 1 year.

Efficacy - Overall Survival

Presented are the counts of patients that have survived up to 2 years.

Secondary Outcome Measures

Full Information

NCT ID

NCT00293397

First Posted

February 16, 2006

Last Updated

June 18, 2018

Sponsor

Yale University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00293397

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Completed

Study Start Date

November 2005 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cancer

Keywords

adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Drug-eluting bead transarterial chemoembolization (DEB-TACE)

Arm Type

Experimental

Arm 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.

Intervention Type

Device

Intervention Name(s)

Drug-eluting beads loaded with doxorubicin hydrochloride

Other Intervention Name(s)

Gelspheres, LC Beads

Intervention Description

Doxorubicin eluting beads

Primary Outcome Measure Information:

Title

Safety

Description

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.

Time Frame

1 month

Title

Safety

Description

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.

Time Frame

6 months

Title

Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria

Description

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.

Time Frame

1 month

Title

Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)

Description

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.

Time Frame

1 month

Title

Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)

Description

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.

Time Frame

6 months

Title

Efficacy - Overall Survival

Description

Presented are the counts of patients that have survived up to 1 year.

Time Frame

1 Year

Title

Efficacy - Overall Survival

Description

Presented are the counts of patients that have survived up to 2 years.

Time Frame

2 Years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey F. Geschwind, MD

Organizational Affiliation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Official's Role

Study Chair

Facility Information:

Facility Name

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231-2410

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20010173

Citation

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.

Results Reference

result

Liver Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial