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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TATE | Experimental | 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. |
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| TACE | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tirapazamine | Drug | Intra-arterial injection into the tumor feeding artery |
| |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Caifang Ni, M.D | The First Affiliated Hospital of Soochow University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China |
Protection of participant privacy
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D000077704 | Tirapazamine |
| ID | Term |
|---|---|
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Transarterial Embolization |
| Procedure |
Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia |
|
|
| TACE | Procedure | 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. |
|
|
| 36 months |
| ORR | objective Response Rate | 36 months |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |