Evaluate the Effect of Tirazamine on Primary Liver Cancer.

Phase 2TerminatedNCT06848556

Zhejiang Raygene Pharmaceuticals Co., Ltd16 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepato Cellular Carcinoma (HCC)

Interventions

tirapazamineDRUG

Intra-arterial injection into the tumor feeding artery

Transarterial EmbolizationPROCEDURE

Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia

TACEPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Outcomes

Primary Outcomes

Peak Plasma Concentration (Cmax)

Part I: One of the Pharmacokinetic Characteristics

Time frame: 24 hours post-first dose

Area under the plasma concentration versus time curve (AUC)

Part I: One of the Pharmacokinetic Characteristics

Time frame: 24 hours post-first dose

Time to Maximum Concentration（Tmax）

Part I: One of the Pharmacokinetic Characteristics

Time frame: 24 hours post-first dose

Terminal Elimination Half-life（T1/2）

Part I: One of the Pharmacokinetic Characteristics

Time frame: 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.

Time frame: 36 months

Secondary Outcomes

OS defined as the time from randomization to death

Time frame: 36 months

The percentage (%) of patients who achieve a complete response (CR) according to the mRECIST criteria after TACE/TATE treatment.

Time frame: 36 months

ORR

objective Response Rate

Time frame: 36 months

Data from ClinicalTrials.gov

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