Carcinoma, Hepatocellular
Conditions
Keywords
Tirapazamine, embolization, TACE, Hepatocellular carcinoma
Brief summary
An open label randomized study to compare TATE versus TACE in patients with intermediate stage Hepatocellular carcinoma who are not suitable for surgical resection or radiofrequency ablation. The primary endpoint is Progression Free Survival. Secondary endpoints including CR rate, Time to embolization failure, Duration of CR, OS, ORR, local control rate, time to local recurrence and duration to local recurrence. The study treatment is to compare Tirapazamine versus doxorubicin when combined with trans-arterial embolization. Study plans to enroll 134 patients in 1:1 randomization for TATE or TACE. MRI will be used to assess efficacy using a central radiological review for the final analysis.
Detailed description
Trans-arterial chemoembolization (TACE) is a standard care of intermediate stage Hepatocellular carcinoma (HCC) for 40 years without much improvement in efficacy. The key reason for lack of progress is that chemotherapy agents are not effective in hypoxia and cancer stem cells are induced under hypoxia. Tirapazamine, a hypoxia activated agent, can potential solve these two problems. This open label randomized trial will be conducted in HCC patients who are in intermediate stage and naive to embolization, Child Pugh up to B7 and with normal organ functions. Patients will be randomized 1:1 to receive TATE (trans-arterial tirapazamine embolization) or conventional TACE. The goal of treatment aims to achieve CR by mRECIST for every patient. If there is evidence of viable lesion, patients should be treated again. All patients are followed by contrast MRI scans every 2 months in the first year and every 3 months afterwards until patients have evidence of progression and no longer considered suitable for TATE/TACE. Survival will be followed for 3 years. Total sample size will be 134 patients with the total study duration for 3 years.
Interventions
DRUGTirapazamine
Replacing the standard chemotherapy agent doxorubicin used in TACE with tirapazamine
DRUGDoxorubicin
Standard of care for TACE
Sponsors
Teclison Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Central radiology reviewers are blinded.
Intervention model description
1:1 randomization, open label with central radiological review
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of HCC by imaging criteria per American Association for the Study of Liver Diseases (AASLD) criteria. 2. Patients with single or multiple HCC who are unsuitable for surgical resection or RFA, but suitable for embolization. 3. ECOG score 0-1. Child-Pugh score up to B7. 4. Patients should have measurable tumor lesion(s) by contrast MRI. 5. Patients have adequate normal organ function and suitable laboratory criteria. 6. Men and women of child-bearing age need to commit to using two levels of contraception simultaneously to avoid pregnancy.
Exclusion criteria
1. Patients who have had a liver transplantation. 2. Patients who have uncontrolled major medical problems such as cardiac, pulmonary (COPD requiring constant oxygen), renal (creatinine over 2.0) diseases, active infectious diseases (except chronic Hepatitis B or C), or non-healing ulceration. 3. Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on room air. 4. Patients with evidence of arterial insufficiency or microangiopathy in any organ due to any reason, which could lead to distal extremity hypoxia, as evidenced by any gangrenous change in distal limbs or requiring resection for this reason. 5. Patients with poorly controlled HBV infection. 6. Patients on interferon treatment need to have at least 2-week washout period from Day 1. 7. Patients with major gastrointestinal bleeding in the prior 2 months of enrollment or known diagnosis of cancer other than HCC. 8. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | within 2 years | mRECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 3 years | From randomization to death |
| Complete Response rate | 2 years | CR rate based on mRECIST criteria |
| Time to Embolization Failure | 1 year | From randomization to stage progression |
| Duration of CR | 1 year | From randomization to recurrence in those patients who achieved CR |
Other
| Measure | Time frame | Description |
|---|---|---|
| Local recurrence rate | 1 year | Recurrence rate in the embolized lesion |
| Time to local recurrence | 2 years | From randomization to local recurrence |
Countries
United States
Outcome results
None listed