Clinical trial NCT02220088: The Efficacy and Safety of Retreatment With TAI for Patients Who Showed TACE-resistant: a Randomized Controlled Trial
Official title: The Efficacy and Safety of Retreatment With Transcatheter Arterial Infusion (TAI) for Patients Who Showed TACE-resistant: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
TACE
TACE failure
TACE refractoriness
TAI
Sorafenib
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Kaiping Central Hospital
name: Guangzhou No.12 People's Hospital
First posted: 2014-08-19
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 1 year
Secondary outcomes:
measure: Number of Adverse Events
timeFrame: 30 days
measure: overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Cancer Center, Sun Yat-set University
name: Ming Shi
role: PRINCIPAL_INVESTIGATOR
References:
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. Cancer Treat Rev. 2011 May;37(3):212-20. doi: 10.1016/j.ctrv.2010.07.006. Epub 2010 Aug 17.
citation: 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. 2012 Nov;32(4):348-59. doi: 10.1055/s-0032-1329906. Epub 2013 Feb 8.
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 Interventions in Hepatocellular Carcinoma (EPOIHCC). Liver Int. 2013 Mar;33(3):327-37. doi: 10.1111/liv.12083. Epub 2013 Jan 18.
citation: Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Muller 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):2261-73. doi: 10.1002/hep.26256. Epub 2013 May 3.
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 carcinoma: Consensus recommendations and review by an International Expert Panel. Liver Int. 2014 Feb;34(2):174-83. doi: 10.1111/liv.12314. Epub 2013 Nov 20.
citation: Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Muller 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 Hepatol. 2014 Jan;60(1):118-26. doi: 10.1016/j.jhep.2013.08.022. Epub 2013 Sep 3.
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. No abstract available.