Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil/Leucovorin Versus Sorafenib in Advanced Hepatocellular Carcinoma

NCT03164382 | Completed Phase 3 DMC

• 1 other identifier: SB5010-2017-015
• Study Type: interventional
• Target: 262
• Locations: 1 country
• Sites: 1

Brief Summary

This trial was designed to investigate whether the survival outcome, response rate and safety of hepatic arterial infusion of oxaliplatin, fluorouracil/leucovorin regimens for patients with Barcelona-Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma was superior than those of the standard treatment with sorafenib or not.

Conditions

Liver Cancer; Hepatic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival was the length of time after treatment until death from any cause.

  1 months

Secondary Outcomes (2)

• Time to Progression

  1 months

• Time to Intrahepatic tumor Progression

  1 months

Study Arms (2)

HAIF group

EXPERIMENTAL

FOLFOX regimen: oxaliplatin 130 mg/m2 on day 1 from hour 0 to 3; leucovorin 200 mg/m2 from hour 3 to 5, fluorouracil 400 mg/m2 bolus at hour 5, and then fluorouracil 2,400 mg/m2 over 46 hours, via hepatic artery, once every 3 weeks.

Drug: FOLFOX regimen

Sorafenib group

ACTIVE COMPARATOR

Sorafenib 200mg Tab, 400 mg twice per day orally. Treatment was given in 4-week cycles.

Drug: Sorafenib 200Mg Tab

Interventions

FOLFOX regimen DRUG

Firstly, the femoral artery was percutaneously punctured using the Seldinger technique. Then, the catheter was inserted into the celiac trunk or superior mesenteric artery for arteriography. When more than one feeding artery of HCC was detected, the smaller arteries were embolized with gelatin sponge particles. A micro-catheter was inserted through the arterial catheter located at the common hepatic artery or proper hepatic arterial branch (feeding artery). When blood flows into the gastroduodenal artery was confirmed by micro-catheter angiography, the route was embolized with a coil or micro-coil to prevent reflux of chemotherapeutic drugs to the stomach and duodenum. The peripheral part of the catheter that was exposed to the outside of the body was covered with medical sterile gauze and fastened on the thigh's skin using medical rubberized fabric and bandage. Catheter insertion was repeatedly performed before every cycle of treatment.

HAIF group

Sorafenib 200Mg Tab DRUG

Sorafenib will be administered orally at the starting dose of 400 mg twice daily (800 mg total daily dose) to patients randomized to Arm S in accordance to its package insert or equivalent documentation. The 400 mg dose will be achieved by administration of 2 x 200 mg film-coated tablets, administered twice daily.

Sorafenib group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures.
• Cytohistological confirmation is required for diagnosis of HCC.
• Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer \[BCLC\] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
• At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Lesions previously treated with local therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be selected unless progression is noted at baseline, in which case, these lesions would be considered as non-target lesions.
• Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.
• Availability of a representative tumor tissue specimen (archival tumor tissue is allowed) at pre-screening.
• Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2.
• Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial.
• Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to procedure:
• Hemoglobin \> 100g/L
• Absolute neutrophil count \>3.0 ×109/L
• Neutrophil count \> 1.5 ×109/L
• Platelet count ≥ 50.0 ×109/L
• Total bilirubin \< 51 μmol/L
• Alanine transaminase (ALT) and aminotransferase (AST) \< 5 x upper limit of normal

You may not qualify if:

• Received any prior systemic chemotherapy or molecular-targeted therapy for HCC such as sorafenib.
• Previous local therapy completed less than 4 weeks prior to the dosing and, if present any related acute toxicity \> grade 1.
• Any contraindications for hepatic arterial infusion procedure:
• Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).
• Renal failure / insufficiency requiring hemo-or peritoneal dialysis.
• Known severe atheromatosis.
• Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
• Patients with any other malignancies within the last 3 years before study start.
• History of HCC tumor rupture.
• Patients with severe encephalopathy.
• Patients with known active bleeding (e.g. from GI ulcers, esophageal varices) within 2 months prior to baseline/screening visit or with history or evidence of inherited bleeding diathesis or coagulopathy.
• Clinically significant (CTC grade 3 or 4) venous or arterial thrombotic disease within past 6 months.
• History of cardiac disease:
• Congestive heart failure \>New York Heart Association (NYHA) class 2 (refer to Appendix 13.9).
• Active coronary artery disease (CAD) (myocardial infarction more than 6 months prior to study entry is allowed).

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Minimally Invasive Interventional Division, Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center,

Guangzhou, Guangdong, 500060, China

Location

Related Publications (2)

• Chen QF, Jiang X, Hu Y, Chen S, Lyu N, Zhao M. Interventional arterial chemotherapy versus sorafenib for advanced hepatocellular carcinoma in China: a health economic evaluation of open-label, randomised, phase 3 study. BMJ Open. 2025 May 27;15(5):e095508. doi: 10.1136/bmjopen-2024-095508.

  PMID: 40436447 DERIVED

• Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). J Clin Oncol. 2022 Feb 10;40(5):468-480. doi: 10.1200/JCO.21.01963. Epub 2021 Dec 14.

  PMID: 34905388 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Folfox protocol; Sorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 21, 2017
• First Posted: May 23, 2017
• Study Start: March 1, 2017
• Primary Completion: October 31, 2020
• Study Completion: November 30, 2020
• Last Updated: December 16, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)