HAIC Combined Withzoledronic Acid for the Prevention of Bone Metastases in Advanced HCC

A Randomized Controlled Study of Hepatic Arterial Infusion Chemotherapy of FOLFOX With or Without Zoledronic Acid for the Prevention of Bone Metastases in Advanced Hepatocellular Carcinoma Staged at BCLC C

Zoledronic acid was initially used for bone metastases in various malignancies. However, it is unknown whether hepatic arterial infusion chemotherapy combined with zoledronic acid can improve overall survival of unresectable hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: HAIC; Drug: Zoledronic acid

• Study Type: Interventional
• Enrollment (Anticipated): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University
      • Contact: Ming Shi, MD; Phone Number: 8620-87343115; Email: shiming@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.
• Unresectable HCC. For BCLC C HCC, sorafenib/lenvatinib or PD-1/L1 antibody was allowed.
• 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.
• Known central nervous system tumors including metastatic brain disease

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: HAIC with zoledronic Acid	Procedure: HAIC; hepatic arterial infusion of oxaliplatin, LV and 5-fu (20h); Drug: Zoledronic acid; Zoledronic acid 4mg iv.drip
Active Comparator: HAIC without zoledronic Acid	Procedure: HAIC; hepatic arterial infusion of oxaliplatin, LV and 5-fu (20h)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	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.	12 months
Objective Response Rate (ORR)	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.	12 months
Adverse Events	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03	30 days

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2023
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; hepatic arterial infusion chemotherapy; zoledronic Acid
• 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; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: S-069

Drug and device information, study documents

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