Phase 2 Study of Sorafenib Plus HAIC of FOLFOX vs. Sorafenib Plus HAIC of OXA for Advanced HCC

Phase 2

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: Sorafenib; Drug: HAIC of OXA; Drug: HAIC of FOLFOX

• Registration Number: NCT03812770
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin compared with HAIC of oxaliplatin alone in patients with advanced hepatocellular carcinoma (HCC)

Detailed Description

Sorafenib is the most widely used palliative treatment for advanced hepatocellular carcinoma (HCC) patients . Our previous prospective study revealed that sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin confer a survival benefit to advanced HCC . However, HAIC of fluorouracil is not such for advanced HCC. Whether HAIC of oxaliplatin is as effective as HAIC of oxaliplatin plus fluorouracil/leucovorin is controversial. Thus, the investigators carried out this prospective randomized control study to find out it.

Study Timeline

• Study Start: 2018-08-04
• Status Verified: 2019-01
• Study First Submitted: 2019-01-19
• Study First Submitted QC: 2019-01-19
• Study First Posted: 2019-01-23
• Last Update Submitted: 2019-04-15
• Last Update Posted: 2019-04-17
• Primary Completion: 2019-09-01
• Study Completion: 2019-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
• Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
• Barcelona clinic liver cancer-stage C
• Eastern Cooperative Oncology Group performance status of 0 to 2
• with no previous treatment
• No Cirrhosis or cirrhotic status of Child-Pugh class A only
• Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
• The following laboratory parameters:

Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 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

• 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.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of bleeding diathesis.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sorafenib plus HAIC of OXA	HAIC of OXA	Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin
Sorafenib plus HAIC of FOLFOX	HAIC of FOLFOX	Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin, Fluorouracil and Leucovorin
Sorafenib plus HAIC of OXA	Sorafenib	Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin
Sorafenib plus HAIC of FOLFOX	Sorafenib	Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin, Fluorouracil and Leucovorin

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	12 months	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	12 months	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.
Adverse Events	30 days	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03
Overall Survival (OS)	12 months	OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.

Trial Locations

Locations (3)

Cancer Center Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Guangzhou Twelfth People 's Hospita; 🇨🇳 Guangzhou, Guangdong, China

Kaiping Central Hospital; 🇨🇳 Kaiping, Guangdong, China