Liver Cancer
Conditions
Keywords
adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer
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.
Interventions
DEVICEDrug-eluting beads loaded with doxorubicin hydrochloride
Doxorubicin eluting beads
Sponsors
National Cancer Institute (NCI)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 1 month | 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 | 1 month | 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) | 1 month | 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 - Overall Survival | 1 Year | Presented are the counts of patients that have survived up to 1 year. |
Countries
United States
Participant flow
Recruitment details
20 patients with unresectable hepatocellular carcinoma (HCC) were enrolled at Johns Hopkins Hospital to undergo treatment with drug-eluting beads (DEBs) infused with doxorubicin. The last patient was enrolled in Dec 2007.
Participants by arm
| Arm | Count |
|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (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.
doxorubicin hydrochloride: Doxorubicin eluting beads | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) |
|---|---|
| Age, Continuous | 64 years |
| Barcelona Clinic Liver Cancer (BCLC) grade BCLC A | 6 Participants |
| Barcelona Clinic Liver Cancer (BCLC) grade BCLC B | 2 Participants |
| Barcelona Clinic Liver Cancer (BCLC) grade BCLC C | 12 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
Primary
Efficacy - Overall Survival
Presented are the counts of patients that have survived up to 1 year.
Time frame: 1 Year
Population: 20 patients were assessed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Overall Survival | 13 Participants |
Primary
Efficacy - Overall Survival
Presented are the counts of patients that have survived up to 2 years.
Time frame: 2 Years
Population: 20 patients were assessed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Overall Survival | 11 Participants |
Primary
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.
Time frame: 1 month
Population: 19 of 20 patients were assessed at 1 month.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 1 month post-TACE : Complete Response (CR) | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 1 month post-TACE : Partial Response (PR) | 2 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 1 month post-TACE : Stable Disease (SD) | 18 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 1 month post-TACE : Progressive Disease | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | Disease control rate (CR + PR + SD) | 19 Participants |
Primary
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.
Time frame: 6 months
Population: 19 of 20 patients were assessed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 6 months post-TACE : Complete Response (CR) | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 6 months post-TACE : Partial Response (PR) | 7 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 6 months post-TACE : Stable Disease (SD) | 11 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 6 months post-TACE : Progressive Disease (PD) | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | Disease control rate (CR + PR + SD) | 19 Participants |
Primary
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.
Time frame: 1 month
Population: 19 of 20 patients were assessed at 1 month.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria | 1 month post-TACE : Complete Response (CR) | 6 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria | 1 month post-TACE : Partial Response (PR) | 6 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria | 1 month post-TACE : Stable Disease (SD) | 8 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria | 1 month post-TACE : Progressive Disease | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria | Disease control rate (CR + PR + SD) | 19 Participants |
Primary
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.
Time frame: 6 months
Population: 19 of 20 patients were assessed at 6 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Safety | Grade 2 | 8 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Safety | Grade 3 | 1 Participants |
Primary
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.
Time frame: 1 month
Population: 19 of 20 patients were assessed at 1 month.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Safety | Grade 2 | 16 Participants |
| Drug-eluting Bead Transarterial Chemoembolziation (DEB-TACE) | Safety | Grade 3 | 3 Participants |