Taiwan ACE Beads for Hepatoma Embolization Therapy

• Sponsor: National Cheng-Kung University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02825550
• Collaborator: The Industrial Technology Research Institute (Other), National Cheng Kung University (Other), National Research Program for Biopharmaceuticals, Taiwan (Other)
• Enrollment: 13
• Location: 1
• Arm: 1
• Actual Duration (Months): 9
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Radiopaque Microsphere (T-ACE Beads) interventional therapy for patients with liver cancer

Condition or Disease	Intervention/Treatment	Phase
Cancer of Liver	Device: Taiwan ACE Beads	N/A

Detailed Description

The study will evaluate the safety and tolerability of Taiwan ACE Beads used for chemoembolization for the treatment of unresectable hepatocellular carcinoma.

The investigators will study the overall response rates of lesions with Taiwan ACE Beads. The procedure is similar with conventional TACE (transcatheter arterial chemoembolization). At the target vessels, radiologists will inject lipiodol with doxorubicin first, then Taiwan ACE Beads instead of Gelfoam or PVA (polyvinyl alcohol). The end point of injection is also similar with conventional TACE.

Determine the complication rates, progression free survival (PFS) and overall survival (OS) following Taiwan ACE Beads embolization.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Radiopaque Microsphere (Hydrophilic Series) for Hepatoma Embolization Therapy
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hepatoma treated using Taiwan ACE Beads The use of Taiwan ACE Beads (T-ACE) microspheres embolization as a treatment for patients with hepatoma.	Device: Taiwan ACE Beads; Similar with conventional TACE, radiologist inject lipiodol with doxorubicin first, then use Taiwan ACE Beads instead of Gelfoam or polyvinyl alcohol.

Outcome Measures

Primary Outcome Measures

1. Patients Survival (Safety) [An average of 12 weeks.]

   Survival rate was evaluated since treatment day until the date of death or final observation.

2. Tumor Response (Efficacy) [Before treatment, one month and three month after T-ACE using CT scan and MRI]

   mRECIST criteria was used to evaluate tumor response in patients with hepatoma who received Taiwan ACE beads (T-ACE) microspheres embolization.

Secondary Outcome Measures

1. Serum Level of AFP [Baseline serum AFP levels compared with one or three months of serum levels of AFP after Taiwan ACE Beads procedure]

   Serum Level of AFP [Time Frame: Baseline serum AFP levels (168±383) compared with one or three months of serum levels of AFP (144±256) after Taiwan ACE Beads procedure]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients must meet all of the following inclusion criteria in order to be entered into the study:

1. Both genders of patients age 18 or older.

2. Patients diagnosed of liver cancer (MUST meet at least ONE of the following criteria:)

1. Diagnosed via tumor biopsy by Pathologists, and confirmed by on-service physician.

2. High risk patients (Viral hepatitis B or C or cirrhotics) with typical liver cancer image appeared on more than two radiographic examinations (Ultrasound, MRI, CT scan or Angiography).

3. High risk patients (Viral hepatitis B or C cirrhotics) with evidence of enlarging image of liver cancer via more than two follow-up records.

1. In intermediate stage by BCLC staging, tumor size between 3 to 6 centimeters, with liver function at Child-Pugh class<9, and is either difficult to accept an operation or reluctant to accept any operation.

2. Disease can be treated by transarterial chemoembolization, and can be evaluated by Ultrasound, Magnetic resonance imaging (MRI), or computed tomography (CT).

3. Performance status ECOG 2 or less. Patient has a life expectancy of at least 3 months.

Exclusion Criteria:

If patients meet any of the following criteria they may not be entered into the study:

1. major branch of portal vein has been invaded already; extrahepatic metastasis or the the other malignant tumors.

2. Evidences of decompensation: Total Bilirubin>2, PT prolong>3 seconds, AST > 500U/L, ALT> 500U/L, Child-Pugh class≧9, refractory ascites, active bleeding, hepatic encephalopathy, and severe infection.

3. Tumor size (diameter) larger than 6 centimeters or smaller than 3 centimeters.

4. Cr>2.0 mg/dL and eGFR<50%.

5. Allergic to iodine or other injections.

6. Other main organ failure (Heart, Lung, or Kidney)

7. WBC<3000, ANC<1500.

8. Performance status ECOG of 3 or more.

9. Unable to follow-up by ultrasound or CT scan.

10. Unwilling to sign a written informed consent form.

11. Pregnant women and breath feeding women.

12. Patients whose blood vessel are too difficult to do Taiwan ACE Beads procedure.

13. Prominent AV shunt.

14. Severe atherosclerosis.

15. Vasospasm or possible major vascular injury.

16. Arteriovenous shunt patients, diameter larger than the size of microsphere available.

17. Collateral vascular exists and may endanger non-targeted area during arterial chemoembolization.

18. Contraindications for doxorubicin.

19. Number of tumors more than 3 and locate at different lobes.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cheng Kung University Hospital	Tainan		Taiwan

Sponsors and Collaborators

• National Cheng-Kung University Hospital
• The Industrial Technology Research Institute
• National Cheng Kung University
• National Research Program for Biopharmaceuticals, Taiwan

Investigators

• Study Director: Xi-Zhang Lin, Department of Internal Medicine, National Cheng Kung University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chen CY, Liu HS, Lin XZ. Hydrodynamics-based gene delivery to the liver by bile duct injection of plasmid DNA--the impact of lasting biliary obstruction and injection volume. Hepatogastroenterology. 2005 Jan-Feb;52(61):25-8.
• Liu YS, Lin XZ, Tsai HM, Tsai HW, Chen GC, Chen SF, Kang JW, Chou CM, Chen CY. Development of biodegradable radiopaque microsphere for arterial embolization-a pig study. World J Radiol. 2015 Aug 28;7(8):212-9. doi: 10.4329/wjr.v7.i8.212.
• Luo TY, Shih YH, Chen CY, Tang IC, Wu YL, Kung HC, Lin WJ, Lin XZ. Evaluating the potential of (188)Re-ECD/lipiodol as a therapeutic radiopharmaceutical by intratumoral injection for hepatoma treatment. Cancer Biother Radiopharm. 2009 Oct;24(5):535-41. doi: 10.1089/cbr.2008.0603.

• Responsible Party: National Cheng-Kung University Hospital
• ClinicalTrials.gov Identifier: NCT02825550
• Other Study ID Numbers: B-BR-104-046
• First Posted: Jul 7, 2016
• Last Update Posted: Aug 7, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by National Cheng-Kung University Hospital: Hepatoma; Transcatheter Arterial chemo-embolization; Microsphere
• Additional relevant MeSH terms: Carcinoma, Hepatocellular; Liver Neoplasms

Study Results

Participant Flow

Recruitment Details	The recruitment started in April, 2016. The location was all taken place in National Cheng Kung University Hospital. Patients who met inclusion criteria were recruited.

Arm/Group Title	Hepatoma Patients Treated With T-ACE Beads
Arm/Group Description	In the Hepatoma Embolization Therapy, the catheter was placed to the appropriate position in tumor-supplying artery. Lipiodol containing doxorubicin were firstly injected, followed by the injection of our T-ACE beads-H series microspheres. The follow-up blood tests and adverse events were conducted afterwards. CT scan or MRI would be scheduled at the first and the third months to evaluate the change of tumor size.
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Hepatoma Treated Using Taiwan ACE Beads
Arm/Group Description	Clinical information of T-ACE beads H-series: Gender Male/Female 7/5, Age 71±8. The initial number of participants in the study was 13. However, one patient's blood test did not meet the standard before the operation, which led to his/her withdrawal from the clinical trial. Consequently, the total number of participants analyzed was 12.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 16.7%
>=65 years	10 83.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71 (8)
Sex: Female, Male (Count of Participants)
Female	5 41.7%
Male	7 58.3%
Region of Enrollment (participants) [Number]
Taiwan	12 100%

Outcome Measures

1. Primary Outcome

Title	Patients Survival (Safety)
Description	Survival rate was evaluated since treatment day until the date of death or final observation.
Time Frame	An average of 12 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hepatoma Treated Using Taiwan ACE Beads
Arm/Group Description	Hepatoma patients received Taiwan ACE Beads (T-ACE) microspheres embolization to treat the tumors. Taiwan ACE Beads: The procedure is similar with conventional TACE. Radiologist inject lipiodol with doxorubicin first, then use Taiwan ACE Beads instead of Gelfoam or polyvinyl alcohol. Survival rate was evaluated since beginning of treatment until date of death or final observation.
Measure Participants	12
Count of Participants [Participants]	12 100%

2. Primary Outcome

Title	Tumor Response (Efficacy)
Description	mRECIST criteria was used to evaluate tumor response in patients with hepatoma who received Taiwan ACE beads (T-ACE) microspheres embolization.
Time Frame	Before treatment, one month and three month after T-ACE using CT scan and MRI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hepatoma Patients Treated With T-ACE Beads
Arm/Group Description	We have 7 male and 5 female patients eligible in this study, HBV 4+1, HCV5+1, non-HBV and non-HCV 2, mean age 71± 8. Two patient received treatment at the first time. The other 10 patients received RFA 13 times, and TACE 23 times, and surgery 2 times. The response of the target lesions are: CR 3 PR 4 SD 3 PD 2 (for target lesions), and CR 2 PR 3 SD 3 PD 4 (for the overall response). Liver function, serological ALT(35±24) had mild elevation on the second day (61±47), but all return to baseline (40±20). AFP decreased from 168± 382 to 156± 264. [Conclusion] Our T-ACE Beads are safe and has some effects in treating hepatoma patients.For further clinical trials, loading appropriate chemotherapeutic agents to our microspheres for TACE is needed.
Measure Participants	12
Complete Remission (CR)	3 25%
Partial Response (PR)	4 33.3%
Stable Disease (SD)	3 25%
Progressive Disease (PD)	2 16.7%
Complete Remission (CR)	2 16.7%
Partial Response (PR)	3 25%
Stable Disease (SD)	3 25%
Progressive Disease (PD)	4 33.3%

3. Secondary Outcome

Title	Serum Level of AFP
Description	Serum Level of AFP [Time Frame: Baseline serum AFP levels (168±383) compared with one or three months of serum levels of AFP (144±256) after Taiwan ACE Beads procedure]
Time Frame	Baseline serum AFP levels compared with one or three months of serum levels of AFP after Taiwan ACE Beads procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hepatoma Treated Using Taiwan ACE Beads
Arm/Group Description	Hepatoma patients received Taiwan ACE Beads (T-ACE) microspheres embolization to treat the tumors. Taiwan ACE Beads: The procedure is similar with conventional TACE. Radiologist inject lipiodol with doxorubicin first, then use Taiwan ACE Beads instead of Gelfoam or polyvinyl alcohol.
Measure Participants	12
Baseline serum AFP levels	168 (383)
one or three months of serum levels of AFP	144 (256)

Adverse Events

Arm/Group Title	Adverse Event
Arm/Group Description	There was no adverse event reported in this trial.
All Cause Mortality
	Adverse Event
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	Adverse Event
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	Adverse Event
	Affected / at Risk (%)	# Events
Total	0/13 (0%)

Limitations/Caveats

Case number : only 12 patients completed trial. Tumor size limited to 3-6 cm only.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.