Sorafenib or Lenvatinib Plus HAIC of 130 mg/m² Oxaliplatin, and 5-fu vs Sorafenib or Lenvatinib Plus HAIC of 85mg/m² Oxaliplatin, and 5-fu for Unresectable Advanced HCC: a Randomised Phase 3 Trial

Sorafenib or Lenvatinib Plus Hepatic Artery Infusion of 130 mg/m² Oxaliplatin, Leucovorin, and Fluorouracil Versus Sorafenib or Lenvatinib Plus Hepatic Artery Infusion of 85 mg/m² Oxaliplatin, Leucovorin, and 1200 mg/m² Fluorouracil for Unresectable Advanced Hepatocellular Carcinoma: a Randomised Phase 3 Trial

A randomized trial showed that sorafenib plus hepatic artery infusion of 85mg/m² oxaliplatin, leucovorin and fluorouracil is more effective than sorafenib in advanced hepatocellular carcinoma. However, a retrospective study showed that hepatic artery infusion of 130 mg/m² oxaliplatin, leucovorin and fluorouracil is more effective than sorafenib in advanced hepatocellular carcinoma. It is unknown which oxaliplatin dose is better.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: HAIC of 130 mg/m² Oxaliplatin, and 5-fu; Drug: TKI; Drug: HAIC of 85 mg/m² Oxaliplatin, and 5-fu

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510620
      • Recruiting
      • Guangzhou Twelfth People 's Hospita
      • Principal Investigator: YuanMin Zhou, MD
    • Kaiping, Guangdong, China, 529300
      • Recruiting
      • Kaiping Central Hospital

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:

• 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).
• Patients must have at least one tumor lesion that can be accurately measured;
• With vascular invasion or extrahepatic metastasis
• Diagnosed as unresectable with consensus by the panel of liver surgery experts;
• No past history of TACE, HAIC, chemotherapy or molecule-targeted treatment;
• No Cirrhosis or cirrhotic status of Child-Pugh class A only

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OXA 130; Patients received sorafenib or lenvatinib Plus HAIC of 130 mg/m² oxaliplatin, and 2400 mg/m² 5-fu	Drug: HAIC of 130 mg/m² Oxaliplatin, and 5-fu; Hepatic arterial infusion of 130 mg/m² oxaliplatin,leucovorin and 2400 mg/m² 5-FU; Drug: TKI; sorafenib 400mg bid or lenvatinib 12 mg/day (for bodyweight ≥60 kg) or 8 mg/day (for bodyweight <60 kg)
Active Comparator: OXA 85; Patients received sorafenib or lenvatinib Plus HAIC of 85 mg/m² oxaliplatin, and 2400 mg/m² 5-fu	Drug: TKI; sorafenib 400mg bid or lenvatinib 12 mg/day (for bodyweight ≥60 kg) or 8 mg/day (for bodyweight <60 kg); Drug: HAIC of 85 mg/m² Oxaliplatin, and 5-fu; Hepatic arterial infusion of 85 mg/m² oxaliplatin,leucovorin and 2400 mg/m² 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival		24 months
objective response rate		6 months
time to response	time to the date that patients achieved objective response	12 months
Adverse Events		30 Days after HAIC

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou No.12 People's Hospital; Kaiping Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 24, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil; Oxaliplatin
• Other Study ID Numbers: SH-3

Drug and device information, study documents

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