Clinical trial NCT06848556: Evaluate the Effect of Tirazamine on Primary Liver Cancer.
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hepato Cellular Carcinoma (HCC)
Keywords: TATE
TACE
pharmacokinetics
HEPATOCELLULAR CARCINOMA
Lead sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2025-02-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: 24 hours post-first dose
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 24 hours post-first dose
measure: Time to Maximum Concentration（Tmax）
timeFrame: 24 hours post-first dose
measure: Terminal Elimination Half-life（T1/2）
timeFrame: 24 hours post-first dose
measure: PFS
timeFrame: 36 months
Secondary outcomes:
measure: OS
timeFrame: 36 months
measure: CR
timeFrame: 36 months
measure: ORR
timeFrame: 36 months
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Caifang Ni, M.D
role: PRINCIPAL_INVESTIGATOR
References: