Prospective Study to Evaluate Safety of Deb-TACE With 100µ Beads in Patients With Non Resectable HCC

• Sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (Other)
• Overall Status: Completed
• CT.gov ID: NCT02670122
• Collaborator: (none)
• Enrollment: 131
• Location: 1
• Actual Duration (Months): 45
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

This is an observational, multicenter, single arm, prospective study to evaluate safety and tolerability of selective and ultraselective drug eluting beads transcatheter intraarterial chemoembolization (DEB-TACE) with up to 3 ml of well calibrated 100 µ microspheres and up to 150 mg of doxorubicin, for the treatment of non resectable hepatocellular carcinoma (HCC).

The hypothesis is that 100 µ beads penetrate deeper into the tumor than those eluting beads with larger volumes without increasing the risk and complications of DEB-TACE.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Device: DEB-TACE

Detailed Description

In this observational, prospective study patients will undergo DEB-TACE and subsequent follow up procedures according to standard clinical practice. The primary aim of the study is to describe treatment safety and tolerability of 100 µ beads in DEB-TACE. As a secondary end-point a description of efficacy parameters will be obtained.

Study Design

• Study Type: Observational
• Actual Enrollment: 131 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prospective, Multicenter, Non Randomized, Single Arm Study to Evaluate Safety of Transarterial Chemoembolization (TACE) With Doxorubicin Eluting 100 µ Microspheres in Patients With Non Resectable Hepatocellular Carcinoma
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Nov 30, 2018
• Actual Study Completion Date: Nov 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Patients with non resectable HCC DEB-TACE with doxorubicin eluting 100 µ microspheres	Device: DEB-TACE; Selective and ultraselective transcatheter intraarterial administration up to 3ml of well calibrated 100µ drug eluting microspheres with up to 150 mg of doxorubicin.

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability [30 days]

   Major and minor complications, procedure related mortality and post-embolisation syndrome after DEB-TACE of non-resectable HCC, using 100-µm doxorubicin-loaded microspheres

Secondary Outcome Measures

1. Tumor Response [6 months, 1 year, 2 year]

   Devascularization pattern in the treated tumor, assessed with the modified RECIST (mRECIST), in the contrast enhanced liver CT or MR obtained during FU.

2. OS [2 years]

   Overall survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with a diagnosis of HCC according to European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) criteria and staged by BCLC criteria

2. Indication for receiving transarterial chemoembolization DEB-TACE with 100 µ microspheres according to usual clinical practice.

3. Able and willing to participate and give their written informed consent.

4. Both genders and ≥ 18 years old.

5. Eastern Cooperative Oncology Group (ECOG) 0

6. Preserved hepatic function (Child-Pugh ≤ B7).

7. No evidence of tumoral invasion in portal vein or main biliary ducts.

8. Able to go through image diagnostic techniques such as CT or MRI.

9. Preserved cardiac and renal function.

10. No concomitant active infections that require antibiotic treatment.

11. Measurable disease according to mRECIST criteria.

12. Life expectancy over 6 months.

Exclusion Criteria:

1. ECOG ≥ 1

2. Child-Pugh ≥B8.

3. Presence of ascitis or encephalopathy

4. Extrahepatic tumoral disease.

5. Tumoral vascular invasion

6. Serum bilirubin>3 mg/dl.

7. Cr Clearance ≤ 60 ml/min

8. If any of the following is contraindicated:

9. Administration of doxorubicin

10. Iodated contrasts

11. CT or MRI procedures

12. Transarterial embolization procedures

13. White blood cells (WBC) < 2000 /mm3

14. Neutrophil count < 1500 /mm3

15. Ejection fraction < 50 %

16. Platelet count < 5 x 104/mm3, international normalized ratio (INR) > 2,0)

17. Transaminases (AST and/or ALT) > 5x upper limit of normal or >250 u/l

18. Known hepatofugal portal vein flow

19. A-V intrahepatic macroscopic fistula

20. Pregnant or breast feeding women.

21. Tumor burden involving more than 50% of the liver.

22. Active bacterial or fungal infection.

23. Other concomitant tumors.

24. Any other condition that according to investigator criteria, contraindicates DEB-TACE.

25. Patients not willing to participate and/or give their written informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Ramón y Cajal	Madrid		Spain	28034

Sponsors and Collaborators

• Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

Investigators

• Principal Investigator: Jose Urbano, MD, PhD,EBIR, HRyC

Study Documents (Full-Text)

• Informed Consent Form - Mar 15, 2015
• Study Protocol and Statistical Analysis Plan - Mar 15, 2015

More Information

Publications

None provided.

• Responsible Party: Jose Urbano Garcia, MD, PhD, EBIR, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• ClinicalTrials.gov Identifier: NCT02670122
• Other Study ID Numbers: FJD-TAN-14-01
• First Posted: Feb 1, 2016
• Last Update Posted: Mar 30, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jose Urbano Garcia, MD, PhD, EBIR, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: Hepatocellular Carcinoma; TACE
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

Participant Flow

Recruitment Details	Prospective inclusion from march 2015 to november 2016 in 10 University Hospitals

Arm/Group Title	Patients With Non Resectable HCC
Arm/Group Description	DEB-TACE with doxorubicin eluting 100 µ microspheres DEB-TACE: Selective and ultraselective transcatheter intraarterial administration up to 3ml of well calibrated 100µ drug eluting microspheres with up to 150 mg of doxorubicin.
Period Title: Overall Study
STARTED	131
COMPLETED	127
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Patients With Non Resectable HCC
Arm/Group Description	DEB-TACE with doxorubicin eluting 100 µ microspheres DEB-TACE: Selective and ultraselective transcatheter intraarterial administration up to 3ml of well calibrated 100µ drug eluting microspheres with up to 150 mg of doxorubicin.
Overall Participants	131
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.64 (10.85)
Sex: Female, Male (Count of Participants)
Female	28 21.4%
Male	103 78.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 2.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	128 97.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Spain	131 100%
Europe	131 100%
Technical success rate (DEB-TACE procedures) [Number]
Number [DEB-TACE procedures]	214

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability
Description	Major and minor complications, procedure related mortality and post-embolisation syndrome after DEB-TACE of non-resectable HCC, using 100-µm doxorubicin-loaded microspheres
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Major Complications	Minor Complications	Procedure Related Mortality	Severe PES
Arm/Group Description	Common Terminology Criteria for Adverse Events 4.03 grade 3 or 4 adverse events	Common Terminology Criteria for Adverse Events 4.03 grade 1 or 2 adverse events	Patients that died due to the DEB-TACE procedure	Severe Post Embolisation Syndrome is when due to the pain and/or fever caused by the DEB TACE procedure requires intravenous analgesia and extend hospital admission.
Measure Participants	131	131	131	131
Count of Participants [Participants]	9 6.9%	29 NaN	0 NaN	12 NaN

2. Secondary Outcome

Title	Tumor Response
Description	Devascularization pattern in the treated tumor, assessed with the modified RECIST (mRECIST), in the contrast enhanced liver CT or MR obtained during FU.
Time Frame	6 months, 1 year, 2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	6 m ORR	12 m ORR	24 m ORR
Arm/Group Description	Objective Response Rate as the sum of complete and partial response rate 6 months after the first DEB-TACE	Objective Response Rate as the sum of complete and partial response rate 12 months after the first DEB-TACE	Objective Response Rate as the sum of complete and partial response rate 24 months after the first DEB-TACE
Measure Participants	118	94	61
Count of Participants [Participants]	90 68.7%	42 NaN	27 NaN

3. Secondary Outcome

Title	OS
Description	Overall survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Patients that completed 2 year follow up. Patients losf for FU and the patients who recieved recieved liver transplantation are censored.

Arm/Group Title	Overall Survival
Arm/Group Description	OS is defined as the cumulative 24-month survival rate.
Measure Participants	109
Median (Inter-Quartile Range) [months]	22

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	CTCAE 4.03 criteria
Arm/Group Title	Adverse Events
Arm/Group Description	Mortality, minor and major adverse events after Tandem-100 DEB-TACE were assessed in accordance with CTCAE 4.03 criteria
All Cause Mortality
	Adverse Events
	Affected / at Risk (%)	# Events
Total	48/131 (36.6%)
Serious Adverse Events
	Adverse Events
	Affected / at Risk (%)	# Events
Total	9/131 (6.9%)
Gastrointestinal disorders
Colitis	1/131 (0.8%)	1
General disorders
HCC rupture and bleeding. Embolization 10h after TACE	1/131 (0.8%)	1
SIRS systemic inflammatory response syndrome, CKD chronic kidney disease. ICU	1/131 (0.8%)	1
Hepatobiliary disorders
Hepatic Abcess	3/131 (2.3%)	3
Cholecistitis, conservative management	2/131 (1.5%)	2
Respiratory, thoracic and mediastinal disorders
Worsening of a severe COPD	1/131 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Adverse Events
	Affected / at Risk (%)	# Events
Total	29/131 (22.1%)
General disorders
Severe PES	12/131 (9.2%)	12
Partial alopecia	1/131 (0.8%)	1
Hepatobiliary disorders
Asymptomatic segmentary bile duct/biliary tree dilatation	8/131 (6.1%)	8
Biloma. Conservative treatment.	1/131 (0.8%)	1
Vascular disorders
Asymtomatic segmental hepatic artery dissection	2/131 (1.5%)	2
big groing hematoma	2/131 (1.5%)	2
Asymptomatic coagulative thrombosis of a segmental portal branch (LWH)	1/131 (0.8%)	1
Asymptomatic segmental hepatic artery perforation	1/131 (0.8%)	1
Periumbilical bruise (non target falciform artery embolization)	1/131 (0.8%)	1

Limitations/Caveats

Lack of a comparative arm using larger or smaller DEBs or a cTACE group. Intratumor doxorubicin doses were calculated according to the mL of injected mirospheres

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.