Trial Outcomes & Findings for TACE Using Doxorubicin-eluting Beads for Patients With HCC and Marginal Hepatic Reserve (NCT NCT02147301)

Results Overview

Best observed radiographic response rate to Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE) by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was defined as number of patients who had CR, PR, or SD as their best observed response divided by total number of patients with at least one available CT or MRI. Definition of mRECIST for Hepatocellular Carcinoma (HCC). Complete response (CR) = Disappearance of any intratumoral arterial enhancement in all target lesions. Partial response (PR)=At least a 30% decrease in sum of diameters of viable (enhancement in arterial phase) target lesions, taking as reference baseline sum of diameters of target lesions. Stable disease (SD)=Any cases that do not qualify for either partial response or progressive disease. Progressive disease (PD)=An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enh

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

17 participants

Primary outcome timeframe

1 year

Results posted on

2019-09-10

Participant Flow

17 patients were enrolled and completed study.

Participant milestones

Participant milestones
Measure	DEB-TACE Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first
Overall Study STARTED	17
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

TACE Using Doxorubicin-eluting Beads for Patients With HCC and Marginal Hepatic Reserve

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DEB-TACE #1 n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first 1st debtace treatment
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants
Age, Continuous	65 years STANDARD_DEVIATION 5 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Best observed radiographic response for all patients who had at least one follow-up cross-sectional imaging study

Best observed radiographic response rate to Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE) by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was defined as number of patients who had CR, PR, or SD as their best observed response divided by total number of patients with at least one available CT or MRI. Definition of mRECIST for Hepatocellular Carcinoma (HCC). Complete response (CR) = Disappearance of any intratumoral arterial enhancement in all target lesions. Partial response (PR)=At least a 30% decrease in sum of diameters of viable (enhancement in arterial phase) target lesions, taking as reference baseline sum of diameters of target lesions. Stable disease (SD)=Any cases that do not qualify for either partial response or progressive disease. Progressive disease (PD)=An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enh

Outcome measures

Outcome measures
Measure	DEB-TACE n=16 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Best Observed Radiographic Response Rate (Measured by mRECIST) Complete response	4 Participants
Best Observed Radiographic Response Rate (Measured by mRECIST) Partial response	6 Participants
Best Observed Radiographic Response Rate (Measured by mRECIST) Stable disease	4 Participants
Best Observed Radiographic Response Rate (Measured by mRECIST) Progressive disease	2 Participants

PRIMARY outcome

Timeframe: 1 year

Number of patients who developed new severe adverse events according to NCI CTCAE version 4.0

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Number of Patients Who Developed New Severe Adverse Events Ascites	1 participants
Number of Patients Who Developed New Severe Adverse Events Edema of limbs	2 participants
Number of Patients Who Developed New Severe Adverse Events Hepatic failure	4 participants
Number of Patients Who Developed New Severe Adverse Events Pain	2 participants
Number of Patients Who Developed New Severe Adverse Events Hyperbilirubinemia	3 participants
Number of Patients Who Developed New Severe Adverse Events AST elevation	3 participants
Number of Patients Who Developed New Severe Adverse Events Hyponatremia	4 participants
Number of Patients Who Developed New Severe Adverse Events Anemia	2 participants
Number of Patients Who Developed New Severe Adverse Events Thrombocytopenia	3 participants
Number of Patients Who Developed New Severe Adverse Events Creatinine elevation	1 participants

SECONDARY outcome

Timeframe: 6 months

Best observed objective radiographic response was defined as the number of patients who had a complete response or partial response divided by total number of evaluable patients. Measured by mRECIST (see mRECIST definition in the description of the primary objective).

Outcome measures

Outcome measures
Measure	DEB-TACE n=16 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Best Observed Objective Radiographic Response by mRECIST	10 participants

SECONDARY outcome

Timeframe: 1 year

Population: months

TTUP is defined as time (months) from the first on-study DEB-TACE to development of radiographic disease progression untreatable by liver-directed percutaneous or surgical methods (by mRECIST).

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Time to Untreatable Progression (TTUP)	9.7 Months Interval 1.4 to 30.4

SECONDARY outcome

Timeframe: 1 year

Time to progression was defined as the period of time from the first on-study DEB-TACE to radiographic disease progression at any site by mRECIST.

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Time to Progression (TTP)	5.6 Months Interval 0.9 to 13.6

SECONDARY outcome

Timeframe: 1 year

Time to hepatic progression (TTHP) was defined as a period of time from the first on-study DEB-TACE till development of radiographic evidence of disease progression in the liver by mRECIST.

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Time to Hepatic Progression (TTHP)	5.9 Months Interval 0.9 to 13.6

SECONDARY outcome

Timeframe: 3 months, 6 months, 12 Months, and 24 months

Progression free survival rate was defined as the number of patients who were alive and free from radiographic progression by mRECIST at pre-defined time periods. PFS rate was calculated at 3 months, 6 months, 12 months, and 24 months

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Progression Free Survival (PFS) Rate 3 months	14 participants
Progression Free Survival (PFS) Rate 6 months	10 participants
Progression Free Survival (PFS) Rate 12 months	6 participants
Progression Free Survival (PFS) Rate 24 months	4 participants

SECONDARY outcome

Timeframe: 1 year

This measure was defined as the number of patients with alpha-fetoprotein (AFP) response with ≥ 50% decline from baseline (in patients with baseline level ≥ 20) after DEB-TACE.

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Proportion of Patients With Alpha-fetoprotein (AFP) Response With ≥ 50% Decline From Baseline	5 participants

SECONDARY outcome

Timeframe: Baseline, 1 month following last planned DEB-TACE

Left ventricular ejection fraction (LVEF) was measured as percent contraction prior to the first DEB-TACE and 1 month following last planned DEB-TACE. Median LVEF and full range were reported.

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Left Ventricular Ejection Fraction (LVEF) Baseline	70 percent contraction Interval 66.0 to 81.0
Left Ventricular Ejection Fraction (LVEF) 1 month following last planned DEB-TACE	68 percent contraction Interval 60.0 to 74.0

SECONDARY outcome

Timeframe: 7 days

Area under curve for doxorubicin concentration in the serum over 7 days was measured by obtaining serum doxorubicin concentration samples at predose, 5 min, 20 min, 40 min, 60 min, 120 min, 6 hours, 24 hours, 7 days time points. A graph of serum doxorubicin concentration over time was then plotted for each of the 17 patients, and the area under the curve for each of the 17 patients was calculated. Pharmacokinetic sampling was performed only during each of the first planned DEB-TACE procedures.

Outcome measures

Outcome measures
Measure	DEB-TACE n=17 Participants Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Median Area Under Curve (AUC)	593 ng/ml-hr Interval 175.0 to 2030.0

Adverse Events

DEB-TACE

Serious events: 13 serious events

Other events: 17 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	DEB-TACE n=17 participants at risk Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
Gastrointestinal disorders Hepatic failure	23.5% 4/17 • 1 year
Gastrointestinal disorders Ascites	5.9% 1/17 • 1 year
Musculoskeletal and connective tissue disorders Edema of legs	11.8% 2/17 • 1 year
Gastrointestinal disorders Hyperbilirubinemia	17.6% 3/17 • 1 year
Gastrointestinal disorders AST elevation	17.6% 3/17 • 1 year
Renal and urinary disorders Hyponatremia	23.5% 4/17 • 1 year
Blood and lymphatic system disorders Anemia	11.8% 2/17 • 1 year
Blood and lymphatic system disorders Thrombocytopenia	17.6% 3/17 • 1 year

Other adverse events

Other adverse events
Measure	DEB-TACE n=17 participants at risk Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first LC Bead: Doxorubicin Eluting Bead Transarterial Chemoembolization (DEB-TACE): Doxorubicin-loaded LC Beads® are administered via a co-axially placed commercially available hepatic artery catheter into hepatic arteries targeted for treatment. Procedure is performed under direct fluoroscopic visualization until stasis of arterial flow is achieved or until a total of 4 ml of microspheres have been administered, whichever occurs first.
General disorders Anorexia	35.3% 6/17 • 1 year
Gastrointestinal disorders Constipation	5.9% 1/17 • 1 year
Gastrointestinal disorders Diarrhea	11.8% 2/17 • 1 year
Respiratory, thoracic and mediastinal disorders Dyspnea	11.8% 2/17 • 1 year
General disorders Fatigue	47.1% 8/17 • 1 year
General disorders Fever	11.8% 2/17 • 1 year
General disorders Hiccoughs	5.9% 1/17 • 1 year
General disorders Insomnia	23.5% 4/17 • 1 year
Gastrointestinal disorders Nausea	41.2% 7/17 • 1 year
Gastrointestinal disorders Abdominal pain	35.3% 6/17 • 1 year
Gastrointestinal disorders ALT elevation	35.3% 6/17 • 1 year
Renal and urinary disorders Creatinine elevation	17.6% 3/17 • 1 year

Additional Information

Curt Johanson

University of California, San Francisco

Phone: 415-353-2310

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place