HAIC Versus TACE for Large and Unresectable Hepatocellular Carcinoma Staged BCLC A/B

The Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Compared With Transarterial Chemoembolization in Patients With Large and Unresectable Hepatocellular Carcinoma Staged BCLC A/B

The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) in patients with large and unresectable hepatocellular carcinoma staged BCLC A/B.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Folfox Protocol; Procedure: Transarterial chemoembolization; Drug: TACE Drug Protocol; Procedure: Hepatic arterial infusion

Detailed Description

Transarterial chemoembolization (TACE) is the most widely used palliative treatment for hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect of TACE for patients with large hepatocellular carcinoma staged BCLC A/B. Our previous prospective study also revealed similar results of large HCC patients treated with TACE. Recently, the results of our preliminary pilot study suggested that, compared with TACE, hepatic arterial infusion chemotherapy (HAIC) may improve tumor response for HCC with large HCC.

Thus, the investigators carried out this prospective nonrandomized control to demonstrate the superiority of HAIC over TACE.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age range from 18-75 years;
• KPS≥70;
• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL), simultaneously staged as BCLC A or BCLC B based on Barcelona Clinic Liver Cancer staging system.
• Patients must have at least one tumor lesion that can be accurately measured;
• Solitary tumor with diameter ≥10cm, invaded both left and right lobe; or multiple tumors, diameter of the largest was more than 7cm.
• Diagnosed as unresectable with consensus by the panel of liver surgery experts;
• Re commanded treated by TAI or TACE with consensus by the panel of liver MDT;
• No past history of TACE, TAI, chemotherapy or molecule-targeted treatment;
• No Cirrhosis or cirrhotic status of Child-Pugh class A only

• No liver protection therapy in 2 weeks before enrolled, and meet the following laboratory parameters:(a) Platelet count ≥ 75,000/μL; (b)Hemoglobin ≥ 8.5 g/dL;(c) Total bilirubin ≤ 30mmol/L;(d) Serum albumin

  ≥ 32 g/L;(e) ASL and AST ≤ 6 x upper limit of normal;(f) Serum creatinine

  ≤ 1.5 x upper limit of normal;(g) INR > 2.3 or PT/APTT within normal limits; (h) 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 clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Known of serious heart disease which can nor endure the treatment such as cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• 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.
• Evidence of bleeding diathesis.
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture
• Known central nervous system tumors including metastatic brain disease
• Poor compliance that can not comply with the course of treatment and follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hepatic arterial infusion chemotherapy; Procedure/Surgery: Hepatic arterial infusion chemotherapy Drug: Folfox Protocol. Hepatic intraarterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin	Drug: Folfox Protocol; oxaliplatin,leucovorin and 5-FU; Other Names: Folfox for TAI; Procedure: Hepatic arterial infusion; A standard hepatic artery catheter was introduced via the femoral artery percutaneously. Selective catheterization of the proper hepatic artery was performed using standard diagnostic catheters and fluoroscopic guidance. In the event of multiple arterial supply(including superior-mesenteric artery), the proportion of the liver supplied by each artery was estimated by the arteriogram. After optimal positioning of the catheter in dominant supplying artery to ensure minimal reflux, the catheter was fixed and connected with infusion tube. In the condition of multiple tumors on both left and right lobe, the gastroduodenal artery was embolized and the catheter was positioned in the hepatic proper artery for infusion. Folfox Protocol were infused through the fixed catheter sequentially
Active Comparator: Transarterial chemoembolization; Procedure/Surgery: Transarterial chemoembolization Drug: TACE Drug Protocol. Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA)	Procedure: Transarterial chemoembolization; Previous procedure was same with hepatic arterial infusion chemotherapy. After optimal positioning of the catheter, TACE Drug Protocol were injected.; Drug: TACE Drug Protocol; lipiodol mixed with chemotherapy drugs(EADM , lobaplatin, and MMC) followed by polyvinyl alcohol particles (PVA); Other Names: Drugs for transarterial chemotherapy and embolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	Best response based on RECIST	16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Postoperative adverse events were graded based on CTCAE v4.03	30 Days after HAIC and TACE
Time to progression		16 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 24, 2017

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Hepatic arterial infusion chemotherapy; Transarterial Chemoembolization; Large and unresectable HCC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: HCC-170206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED