Evaluate the Effect of Tirazamine on Primary Liver Cancer.

Phase 1

Terminated

• Conditions: Hepato Cellular Carcinoma (HCC)
• Interventions: Drug: tirapazamine; Procedure: TACE; Procedure: Transarterial Embolization

• Registration Number: NCT06848556
• Lead Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

Brief Summary

This Phase I/II trial aims to evaluate the pharmacokinetics, efficacy, and safety of tirapazamine administered via hepatic artery injection followed by TACE in patients with intermediate-stage HCC. The trial will compare the outcomes of TATE with standard TACE.

Detailed Description

The clinical trial is bifurcated into two distinct strata.

Phase One:

This stratum is designed to elucidate the pharmacokinetics of Tirapazamine, specifically its concentration in peripheral blood, in patients with hepatocellular carcinoma (HCC) subsequent to hepatic arterial infusion of Tirapazamine at dosages of 5, 10, and 20 mg/m², culminating in hepatic arterial embolization. A total of approximately 12 patients are slated for enrollment, with 3 to 6 patients allocated to each dosage tier. This constitutes a multicenter, open-label, dose-escalation study. Initiation occurs at a Tirapazamine dosage of 5 mg/m² (administered to 3 patients), followed by escalation to 10 mg/m² (administered to 3 patients), and culminating at 20 mg/m² (administered to 6 patients). All subjects undergo hepatic arterial infusion of Tirapazamine directed towards the tumor vasculature, followed by embolization utilizing a formulation comprising iodized oil, gelatin sponge, and contrast agent (the preparation and application of the embolic agent are delineated in Appendix E).

Phase Two:

Phase Two is delineated as a Phase II open-label, randomized, controlled trial that compares the therapeutic outcomes of TATE (Transarterial Tirapazamine Embolization) and TACE (Transarterial Chemoembolization) in patients with intermediate-stage primary hepatocellular carcinoma who are candidates for hepatic arterial embolization. This phase may be conducted contemporaneously with Phase One. Approximately 200 patients will be randomized in a 1:1 ratio to either the experimental arm (Group A, TATE ) or the control arm (Group B, TACE ). Inter-arm crossover is proscribed.

Study Timeline

• Study Start: 2021-05-14
• Primary Completion: 2023-11-06
• Study Completion: 2023-11-20
• Status Verified: 2025-02
• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-02-24
• Last Update Submitted: 2025-02-24
• Study First Posted: 2025-02-27
• Last Update Posted: 2025-02-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Hepatocellular carcinoma, either histologically/cytologically confirmed or clinically diagnosed
• Age 18-80 years
• Patient is eligible to do TAE or TACE treatment.
• ECOG performance status score 0-1.
• Child-Pugh score 5 - 7 .
• No portal vein tumor thrombus, lymph node metastasis, peritoneal tumor seeding, or extrahepatic metastasis.

Exclusion Criteria

• Prior liver transplantation
• History of liver tumor embolization or radioembolization
• Uncontrolled HBV or HCV infection
• Significant cardiovascular, pulmonary, or renal disease
• QTc prolongation or use of QTc-prolonging medications

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TATE	tirapazamine	Part one is a multicenter, open-label, dose-escalation clinical trial. The starting dose of Tirapazamine was 5 mg/m² (for 3 patients), followed by 10 mg/m² (for 3 patients) and 20 mg/m² (for 6 patients). All patients received Tirapazamine injected into the hepatic artery that supplies the tumor, followed by an injection of iodized oil, a mixture of gelatin sponge and contrast agent to complete the embolization. Part Two is a Phase II open-label, randomized, controlled trial. Patients in the experimental group (Group A) will using a fixed dose of 35 mg of tirapazamine injected into the hepatic artery that supplies the tumor, followed by an injection of iodized oil, a mixture of gelatin sponge and contrast agent to complete the embolization.
TATE	Transarterial Embolization	Part one is a multicenter, open-label, dose-escalation clinical trial. The starting dose of Tirapazamine was 5 mg/m² (for 3 patients), followed by 10 mg/m² (for 3 patients) and 20 mg/m² (for 6 patients). All patients received Tirapazamine injected into the hepatic artery that supplies the tumor, followed by an injection of iodized oil, a mixture of gelatin sponge and contrast agent to complete the embolization. Part Two is a Phase II open-label, randomized, controlled trial. Patients in the experimental group (Group A) will using a fixed dose of 35 mg of tirapazamine injected into the hepatic artery that supplies the tumor, followed by an injection of iodized oil, a mixture of gelatin sponge and contrast agent to complete the embolization.
TACE	TACE	Part Two: Patients in the control group (Group B) received standard Transarterial Chemoembolization (TACE) with intra-arterial injection of a mixture of epirubicin and iodized oil at a personalized dose, followed by embolization completed by injecting a suspension of gelatin sponge and contrast agent.

Primary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	24 hours post-first dose	Part I: One of the Pharmacokinetic Characteristics
Area under the plasma concentration versus time curve (AUC)	24 hours post-first dose	Part I: One of the Pharmacokinetic Characteristics
Time to Maximum Concentration（Tmax）	24 hours post-first dose	Part I: One of the Pharmacokinetic Characteristics
Terminal Elimination Half-life（T1/2）	24 hours post-first dose	Part I: One of the Pharmacokinetic Characteristics
PFS	36 months	Part two: Compare the difference in progression-free survival of patients after TATE/TACE treatment to evaluate whether TATE is superior to traditional TACE.

Secondary Outcome Measures

Name	Time	Method
CR	36 months	The percentage (%) of patients who achieve a complete response (CR) according to the mRECIST criteria after TACE/TATE treatment.
ORR	36 months	objective Response Rate
OS	36 months	OS defined as the time from randomization to death

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China