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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05866172

Collaborator

(none)

264

Enrollment

Location

Arms

24.7

Anticipated Duration (Months)

10.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Procedure: HAIC Drug: Zoledronic acid	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

264 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 10, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

overall survival [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.

Secondary Outcome Measures

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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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