Hepato Cellular Carcinoma (HCC)
Conditions
Keywords
TATE, TACE, pharmacokinetics, HEPATOCELLULAR CARCINOMA
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.
Interventions
DRUGtirapazamine
Intra-arterial injection into the tumor feeding artery
PROCEDURETransarterial Embolization
Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia
PROCEDURETACE
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.
Sponsors
Zhejiang Raygene Pharmaceuticals Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 36 months | Part two: Compare the difference in progression-free survival of patients after TATE/TACE treatment to evaluate whether TATE is superior to traditional TACE. |
| Area under the plasma concentration versus time curve (AUC) | 24 hours post-first dose | Part I: One of the Pharmacokinetic Characteristics |
| Time to Maximum Concentration（Tmax） | 24 hours post-first dose | Part I: One of the Pharmacokinetic Characteristics |
| Terminal Elimination Half-life（T1/2） | 24 hours post-first dose | Part I: One of the Pharmacokinetic Characteristics |
| Peak Plasma Concentration (Cmax) | 24 hours post-first dose | Part I: One of the Pharmacokinetic Characteristics |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR | 36 months | The percentage (%) of patients who achieve a complete response (CR) according to the mRECIST criteria after TACE/TATE treatment. |
| ORR | 36 months | objective Response Rate |
| OS | 36 months | OS defined as the time from randomization to death |
Countries
China
Outcome results
None listed