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

NCT02174549 | Recruiting Phase 1 DMC

• 1 other identifier: LT001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hepatocellular Carcinoma; Gastrointestinal Cancer Metastatic; Neuroendocrine Tumors

Keywords

Hypoxia; Embolization; Tirapazamine

Outcome Measures

Primary Outcomes (1)

• Overall Response rate (ORR) by RECIST

  Overall Response Rate by RECIST criteria

  2 years

Secondary Outcomes (2)

• Overall Response Rate

  2 years

• Duration of Response

  2 years

Other Outcomes (2)

• Response Rate in TATE-treated target lesions

  2 years

• Progressive Free Survival

  2 years

Study Arms (1)

Tirapazamine

EXPERIMENTAL

Intra-arterial administration with tirapazamine before embolization to evaluate the response in metastatic liver lesions of NET

Drug: Tirapazamine; Procedure: Conventional Transarterial Embolization (TAE)

Interventions

Tirapazamine DRUG

Intra-arterial injection into the tumor feeding artery

Tirapazamine

Conventional Transarterial Embolization (TAE) PROCEDURE

Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia

Also known as: TAE conducted with Lipiodol and Surgifoam as the embolizing agents.

Tirapazamine

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• No limitation in hepatic lesion tumor size or number but the total volume of liver tumors cannot exceed 50% of the liver volume.
• 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.
• Age 20 or higher, ECOG functional status 0-1, and with no known major cardiac, pulmonary, or renal dysfunction.
• Are candidates for TAE or TACE and without portal vein occlusion per treating interventional radiologists.
• 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.
• 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.

Sponsors & Collaborators

• Teclison Ltd.: lead

Study Sites (2)

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (1)

• Abi-Jaoudeh N, Dayyani F, Chen PJ, Fernando D, Fidelman N, Javan H, Liang PC, Hwang JI, Imagawa DK. Phase I Trial on Arterial Embolization with Hypoxia Activated Tirapazamine for Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021 May 17;8:421-434. doi: 10.2147/JHC.S304275. eCollection 2021.

  PMID: 34041204 BACKGROUND

Related Links

• Phase 1 dose escalation result in Hepatocellular carcinoma

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neuroendocrine Tumors; Hypoxia

Interventions

Tirapazamine; Ethiodized Oil

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Iodized Oil; Plant Oils; Oils; Lipids; Plant Preparations; Biological Products; Complex Mixtures

Study Officials

• Michael Soulen, MD

  Univ. of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ray Lee

CONTACT

info@teclison.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, dose escalation 3+3 design completed; now only for expansion cohort in neuroendocrine tumor.

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 25, 2014
• Study Start: September 1, 2014
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)