Dose-defining Study of Tirapazamine Combined With Embolization in Liver Cancer

April 15, 2026 updated by: Teclison Ltd.

Phase I Dose-Escalating Study of Combining Intravenous Tirapazamine and Transarterial Embolization (TAE) in Liver Cancer

This phase 1 study is to determine the optimal dose and tolerability of a hypoxia-activating agent, tirapazamine, when it is combined with embolization in liver cancer. Liver cancer patients who are Child-Pugh score A, suitable for embolization with tumor no more than 4 nodules are eligible. Tirapazamine will be given by intra-arterial injection before embolization. Treatment effect is evaluated by MRI based on mRECIST criteria. Repeat treatment is necessary only if disease progression. Dose escalation cohort has been completed. Expansion cohort is open for metastatic liver dominant neuroendocrine tumor.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study is a 3+3 design for dose escalation. Each cohort will have 3-6 patients based on tolerability. Patients will receive escalated doses of tirapazamine until maximally tolerated dose. Embolization is performed per standard practice using Lipiodol and Gelfoam under X-ray guidance. Once a suitable dose is determined, an expansion cohort of 15 patients will be treated with the recommended phase 2 dose to determine preliminary efficacy. Expansion cohorts include (1) hepatocellular carcinoma, (2) metastatic solid tumors with liver metastasis, and (3) neuroendocrine tumor. Adverse events are evaluated by CTCAE vs. 5.0 and efficacy is evaluated by MRI using modified RECIST criteria and RECIST criteria.

The dose escalation part has been completed. Only the third cohort or neuroendocrine tumor remains active for future patient enrollment.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
    • Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients with well-differentiated NET and liver-dominant metastatic disease with intrahepatic disease progression, regardless of primary tumor origin or tumor functional status. Patients may have extrahepatic lesions as long as the majority of the disease burden is intrahepatic.
  2. No limitation in hepatic lesion tumor size or number but the total volume of liver tumors cannot exceed 50% of the liver volume.
  3. Patients are allowed to have prior US Food and Drug Administration (FDA)-approved treatments, including systemic therapies, surgery, ablation, or transarterial therapies for the metastatic NET.
  4. Age 20 or higher, ECOG functional status 0-1, and with no known major cardiac, pulmonary, or renal dysfunction.
  5. Are candidates for TAE or TACE and without portal vein occlusion per treating interventional radiologists.
  6. ANC no less than 1000 /μL. Hemoglobin ≥ 9 gm/dL. Platelets no less than 50,000 /μL. Creatinine no more than 2.0 mg/dL. AST, ALT no more than 5X upper limit of normal. Bilirubin no more than 2.5 mg/dl. PT prolongation ≤ 4 sec above upper limit of normal.
  7. Woman of child-bearing potential (WOCBP) should use highly effective contraception during trial participation and for 6 months after the last dose of tirapazamine and men who are partners with WOCBP should use highly effective contraception, including barrier contraception, during trial participation and for 3 months after the last dose of tirapazamine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tirapazamine
Intra-arterial administration with tirapazamine before embolization to evaluate the response in metastatic liver lesions of NET
Drug: Tirapazamine
Intra-arterial injection into the tumor feeding artery
Procedure: Conventional Transarterial Embolization (TAE)
Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia
Other Names:
  • TAE conducted with Lipiodol and Surgifoam as the embolizing agents.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response rate (ORR) by RECIST
Time Frame: 2 years
Overall Response Rate by RECIST criteria
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 2 years
Overall Response Rate by mRECIST criteria
2 years
Duration of Response
Time Frame: 2 years
Duration of Response by RECIST and mRECIST
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate in TATE-treated target lesions
Time Frame: 2 years
by mRECIST and RECIST
2 years
Progressive Free Survival
Time Frame: 2 years
by RECIST and mRECIST
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Teclison Ltd.

Investigators

  • Principal Investigator: Michael Soulen, MD, Univ. of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

September 30, 2028

Study Registration Dates

First Submitted

June 10, 2014

First Submitted That Met QC Criteria

June 23, 2014

First Posted (Estimated)

June 25, 2014

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LT001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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