Evaluate the Effect of Tirazamine on Primary Liver Cancer.

A Multicenter, Randomized, Controlled, Open-label Phase I/II Study to Evaluate the Pharmacokinetics of Transarterial Tirapazamine Embolization for Intermediate-stage Hepatocellular Carcinoma, and Compare Its Efficacy and Safety with Transarterial Chemoembolization

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.

Study Overview

• Status: Terminated
• Conditions: Hepato Cellular Carcinoma (HCC)
• Intervention / Treatment: Drug: tirapazamine; Procedure: Transarterial Embolization; Procedure: 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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TATE; 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.	Drug: tirapazamine; Intra-arterial injection into the tumor feeding artery; Procedure: Transarterial Embolization; Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia; Other Names: TAE
Experimental: 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.	Procedure: TACE; Patients 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.; Other Names: Transarterial Chemoembolization

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd
• Investigators: Principal Investigator: Caifang Ni, M.D, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): November 6, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetics; TACE; HEPATOCELLULAR CARCINOMA; TATE
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Tirapazamine
• Other Study ID Numbers: LT005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Protection of participant privacy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No