Phase Ⅱ Study of HAIC of FOLFOX vs. Sorafenib in HCC Refractory to TACE

Randomized Phase Ⅱ Study of Second-line Treatment Comparing Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, 5-fluorouracil and Leucovorin With Sorafenib in Hepatocellular Carcinoma Refractory to Transarterial Chemoembolization

To evaluate safety and efficacy of combined hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin and sorafenib in hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization(TACE)

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sorafenib; Drug: HAIC of FOLFOX

Detailed Description

In most current guidelines, sorafenib is considered as the second-line treatment for patients with transarterial chemoembolization(TACE) failure or refractoriness.However,the median overall survival of those treated with sorafenib monotherapy was 16.4 to 24.7 months.

Whether combining sorafenib with hepatic arterial infusion chemotherapy(HAIC) of oxaliplatin,5-fluorouracil and leucovorin is safe, well tolerated, and efficacious remains unknown, with no prospective clinical data currently available.The investigators therefore conducted a prospective and randomized phase II trial to compare the safety and efficacy of HAIC with sorafenib in patients refractory to TACE

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510620
      • Guangzhou Twelfth People 's Hospital
    • Guangzhou, Guangdong, China
      • Ming Shi
    • Kaiping, Guangdong, China, 529300
      • Kaiping Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• TACE failure or refractoriness based on the Liver Cancer Study Group of Japan (LCSGJ) criteria, including appearance of vascular invasion or two or more consecutive insufficient responses of the intrahepatic lesion;
• Except for TACE, patients have received no previous anti-tumor treatment;
• The diagnosis of HCC was based on histological results;
• Patients must have at least one tumor lesion that can be accurately measured;
• Not amendable to surgical resection ,local ablative therapy and any other cured 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 ≤ 5 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC of FOLFOX; Hepatic arterial infusion chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil	Drug: HAIC of FOLFOX; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries; Other Names: Oxaliplatin , fluorouracil, and leucovorin
Active Comparator: Sorafenib; Sorafenib 400 mg orally twice a day	Drug: Sorafenib; administration of Sorafenib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The period from the date of the start of HAIC or sorafenib until the date of the confirmation of tumor progression or death	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The period from the date of the start of HAIC or sorafenib until the date of the confirmation of tumor progression or death	12 months
Adverse Events	Postoperative adverse events were graded based on CTCAE v4.03	30 Days after HAIC and TACE
Objective response rate	Best response based on mRECIST	12 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou No.12 People's Hospital; Kaiping Central Hospital
• Investigators: Principal Investigator: Ming Shi, MD, The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Estimated): March 22, 2021
• Study Completion (Estimated): March 22, 2021

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 9, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Sorafenib; Hepatic arterial infusion chemotherapy
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Protein Kinase Inhibitors; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Sorafenib; Oxaliplatin; Leucovorin
• Other Study ID Numbers: HCC-H171011

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No