Evaluate the Effect of Tirazamine on Primary Liver Cancer.

Zhejiang Raygene Pharmaceuticals Co., Ltd

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Hepato Cellular Carcinoma (HCC)

Treatments: Drug: tirapazamine; Procedure: TACE; Procedure: Transarterial Embolization

Study type: Interventional

Funder types: Industry

Identifiers

NCT06848556

LT005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

TATE

Experimental group

Description:

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.

Treatment:

Procedure: Transarterial Embolization

Drug: tirapazamine

TACE

Experimental group

Description:

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.

Treatment:

Procedure: TACE