The Efficacy and Safety of Retreatment With TAI for Patients Who Showed TACE-resistant: a Randomized Controlled Trial

Hepatocellular Carcinoma Clinical Trial

Official title:

The Efficacy and Safety of Retreatment With Transcatheter Arterial Infusion (TAI) for Patients Who Showed TACE-resistant: a Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02220088
• Other study ID #: HCC201408
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 2014
• Est. completion date: July 2018

Study information

• Verified date: December 2018
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, any treatment guidelines do not specify the criteria for repeating TACE. The study,conducted in Europe ，recently published in the journal of Hepatology shows the ART score of >=2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions. However,in clinical practice，we also found some patients who showed TACE-resistant at the beginning of treatment may access to get objective response of retreatment with transcatheter arterial infusion (TAI). So the investigators conduct this prospective,randomized controlled study to find out whether the patient who showed TACE-resistant can obtain survival benefit from retreatment with TAI.

Description:

Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology.This suggests that not all patients with intermediate-stage HCC will derive similar benefit from transcatheter arterial infusion (TAI), and that some patients may benefit from other treatment options.

Repetition of TACE is based on evidence suggesting that one cycle of TACE may not be sufficient for effective treatment of intermediate-stage HCC and repeating TACE prolongs survival. However, intermediate-stage HCC patients often have unsatisfactory clinical outcomes with repeated TACE and there is not sufficiently addressed by existing guidelines include the criteria for repeating TACE and recommendations about the number of TACE cycles to be repeated before switching to another or no treatment.The study,recently published in the journal of Hepatology shows the ART score of >=2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions.In clinical practice，however, we also found some patients who showed TACE-resistant at the beginning of treatment may access to get objective response of retreatment with TAI. So we conduct this prospective,randomized controlled study to find out whether the patient who showed TACE-resistant can obtain survival benefit from retreatment with TAI.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 79
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female patients, > 18 years and <=70 years old diagnosed with HCC according to the European Association for the Study of the Liver (EASL) diagnostic criteria

• The patient has received 2 session of TACE

• TACE failure/refractoriness by Liver Cancer Study Group of Japan (LCSGJ) criteria

• Cirrhotic status of Child-Pugh class A

• The following laboratory parameters:

• Platelet count = 60,000/µL

• Hemoglobin = 8.5 g/dL

• Total bilirubin = 1.5 mg/dL Serum albumin = 35 g/L

• ASL and AST = 5 x upper limit of normal

• Serum creatinine = 1.5 x upper limit of normal

• INR = 1.5 or PT/APTT within normal limits

• Absolute neutrophil count (ANC) >1,500/mm3

• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Patients with complete response (CR) after the first TACE did not receive a further TACE session

• Eastern Cooperative Oncology Group (ECOG) >1

• Known history of HIV

• History of organ allograft

• Known or suspected allergy to the investigational agents or any agent given in association with this trial.

• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.

• Serious non-healing wound, ulcer, or bone fracture

• Evidence of bleeding diathesis.

• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug

• Severe Arterioportal Shunts or Arteriavein Shunts

• Known metastatic disease

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• TAI of FOLFOX
Retreatment with TAI: administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries

Drug:
• Sorafenib
Accept sorafenib.

Locations

Country	Name	City	State
China	Cancer Center Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	Guangzhou No.12 People's Hospital, Kaiping Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. — View Citation

Cheng AL, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Park JW. Re-evaluating transarterial chemoembolization for the treatment of hepatocellular c — View Citation

Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M. The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J — View Citation

Park JW, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Cheng AL. Consensus recommendations and review by an International Expert Panel on Interventi — View Citation

Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, Lencioni R. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Can — View Citation

Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Trauner M, Peck-Radosavljevic M. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology. 2013 Jun;57(6):22 — View Citation

Yousuf F, Cross TJ, Palmer D. The ART strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014 Jul;61(1):175. doi: 10.1016/j.jhep.2014.02.032. Epub 2014 Mar 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		1 year
Secondary	Number of Adverse Events	All severe adverse events for the entire course of treatment	30 days
Secondary	overall survival		1 year