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TATE Versus TACE in Intermediate Stage HCC (TATE)

Primary Purpose

Carcinoma, Hepatocellular

Status

Suspended

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tirapazamine

Doxorubicin

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Tirapazamine, embolization, TACE, Hepatocellular carcinoma

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Confirmed diagnosis of HCC by imaging criteria per American Association for the Study of Liver Diseases (AASLD) criteria.
Patients with single or multiple HCC who are unsuitable for surgical resection or RFA, but suitable for embolization.
ECOG score 0-1. Child-Pugh score up to B7.
Patients should have measurable tumor lesion(s) by contrast MRI.
Patients have adequate normal organ function and suitable laboratory criteria.
Men and women of child-bearing age need to commit to using two levels of contraception simultaneously to avoid pregnancy.

Exclusion Criteria:

Patients who have had a liver transplantation.
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.
Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on room air.
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.
Patients with poorly controlled HBV infection.
Patients on interferon treatment need to have at least 2-week washout period from Day 1.
Patients with major gastrointestinal bleeding in the prior 2 months of enrollment or known diagnosis of cancer other than HCC.
Pregnant or lactating women.

Sites / Locations

University of California, Irvine
Oregon Health Science University
Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Trans-Arterial Tirapazamine Embolization (TATE)

Trans-Arterial ChemoEmbolization (TACE)

Arm Description

Patients will receive a fixed dose of Tirapazamine combined with embolization using Lipiodol and Gelfoam.

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.

Outcomes

Primary Outcome Measures

Progression Free Survival

mRECIST criteria

Secondary Outcome Measures

Overall survival

From randomization to death

Complete Response rate

CR rate based on mRECIST criteria

Time to Embolization Failure

From randomization to stage progression

Duration of CR

From randomization to recurrence in those patients who achieved CR

Full Information

NCT ID

NCT03145558

First Posted

May 3, 2017

Last Updated

November 1, 2022

Sponsor

Teclison Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03145558

Brief Title

TATE Versus TACE in Intermediate Stage HCC

Acronym

TATE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Suspended

Why Stopped

on hold by sponsor

Study Start Date

December 5, 2017 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Teclison Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Hepatocellular

Keywords

Tirapazamine, embolization, TACE, Hepatocellular carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

1:1 randomization, open label with central radiological review

Masking

Outcomes Assessor

Masking Description

Central radiology reviewers are blinded.

Allocation

Randomized

Enrollment

134 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Trans-Arterial Tirapazamine Embolization (TATE)

Arm Type

Experimental

Arm Description

Patients will receive a fixed dose of Tirapazamine combined with embolization using Lipiodol and Gelfoam.

Arm Title

Trans-Arterial ChemoEmbolization (TACE)

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Tirapazamine

Intervention Description

Replacing the standard chemotherapy agent doxorubicin used in TACE with tirapazamine

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

Standard of care for TACE

Primary Outcome Measure Information:

Title

Progression Free Survival

Description

mRECIST criteria

Time Frame

within 2 years

Secondary Outcome Measure Information:

Title

Overall survival

Description

From randomization to death

Time Frame

3 years

Title

Complete Response rate

Description

CR rate based on mRECIST criteria

Time Frame

2 years

Title

Time to Embolization Failure

Description

From randomization to stage progression

Time Frame

1 year

Title

Duration of CR

Description

From randomization to recurrence in those patients who achieved CR

Time Frame

1 year

Other Pre-specified Outcome Measures:

Title

Local recurrence rate

Description

Recurrence rate in the embolized lesion

Time Frame

1 year

Title

Time to local recurrence

Description

From randomization to local recurrence

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Confirmed diagnosis of HCC by imaging criteria per American Association for the Study of Liver Diseases (AASLD) criteria. Patients with single or multiple HCC who are unsuitable for surgical resection or RFA, but suitable for embolization. ECOG score 0-1. Child-Pugh score up to B7. Patients should have measurable tumor lesion(s) by contrast MRI. Patients have adequate normal organ function and suitable laboratory criteria. Men and women of child-bearing age need to commit to using two levels of contraception simultaneously to avoid pregnancy. Exclusion Criteria: Patients who have had a liver transplantation. 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. Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on room air. 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. Patients with poorly controlled HBV infection. Patients on interferon treatment need to have at least 2-week washout period from Day 1. Patients with major gastrointestinal bleeding in the prior 2 months of enrollment or known diagnosis of cancer other than HCC. Pregnant or lactating women.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nadine Abi-Jaoudeh

Organizational Affiliation

University of California, Irvine

Official's Role

Study Chair

Facility Information:

Facility Name

University of California, Irvine

City

Irvine

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Oregon Health Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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TATE Versus TACE in Intermediate Stage HCC

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