TATE Versus TACE in Intermediate Stage HCC (TATE)

TATE Versus TACE, an Open-label Randomized Study Comparing TransArterial Tirapazamine Embolization Versus TransArterial ChemoEmbolization in Intermediate Stage Hepatocellular Carcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Tirapazamine; Drug: Doxorubicin

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92868
      • University of California, Irvine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trans-Arterial Tirapazamine Embolization (TATE); Patients will receive a fixed dose of Tirapazamine combined with embolization using Lipiodol and Gelfoam.	Drug: Tirapazamine; Replacing the standard chemotherapy agent doxorubicin used in TACE with tirapazamine
Active Comparator: Trans-Arterial ChemoEmbolization (TACE); Patients will receive a mixture of doxorubicin and Lipiodol into the tumor feeding artery followed by injection of Gelfoam to induce embolization per standard procedure.	Drug: Doxorubicin; Standard of care for TACE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	mRECIST criteria	within 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From randomization to death	3 years
Complete Response rate	CR rate based on mRECIST criteria	2 years
Time to Embolization Failure	From randomization to stage progression	1 year
Duration of CR	From randomization to recurrence in those patients who achieved CR	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence rate	Recurrence rate in the embolized lesion	1 year
Time to local recurrence	From randomization to local recurrence	2 years

Collaborators and Investigators

• Sponsor: Teclison Ltd.
• Investigators: Study Chair: Nadine Abi-Jaoudeh, University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2017
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: May 3, 2017
• First Submitted That Met QC Criteria: May 4, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Tirapazamine, embolization, TACE, Hepatocellular carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antibiotics, Antineoplastic; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Tirapazamine; Doxorubicin
• Other Study ID Numbers: LT-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No