Combining tirapazamine with embolization for liver cancer treatment

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

This study is testing a new way to treat liver cancer by combining a drug called tirapazamine with a procedure called embolization to see how well it works and how much of the drug can be safely given to patients.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 20 Years to 99 Years
• Sex: All
• Sponsor: Teclison Ltd. (Industry-sponsored)
• Locations: 2 sites (Palo Alto, California and 1 other locations)
• Trial ID: NCT02174549 on ClinicalTrials.gov

What this trial studies

This phase 1 and 2 clinical trial aims to determine the optimal dose and tolerability of tirapazamine, a hypoxia-activating agent, when used in conjunction with embolization for patients with liver cancer. The study employs a 3+3 dose escalation design to identify the maximum tolerated dose, followed by an expansion cohort to assess preliminary efficacy in specific patient populations, including those with hepatocellular carcinoma and neuroendocrine tumors. Treatment involves intra-arterial injection of tirapazamine prior to embolization, with efficacy evaluated through MRI based on modified RECIST criteria. The trial is currently focused on patients with liver-dominant metastatic neuroendocrine tumors.

Who should consider this trial

Good fit: Ideal candidates include adults aged 20 or older with well-differentiated neuroendocrine tumors that are liver-dominant and have shown intrahepatic disease progression.

Not a fit: Patients with significant extrahepatic disease burden or those with major cardiac, pulmonary, or renal dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with liver cancer, potentially improving outcomes and quality of life.

How similar studies have performed: While the combination of tirapazamine and embolization is a novel approach, similar studies involving hypoxia-activated therapies have shown promise in other cancer types.

Eligibility criteria

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.

Where this trial is running

Palo Alto, California and 1 other locations

• Stanford University — Palo Alto, California, United States (Recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Michael Soulen, MD — Univ. of Pennsylvania
• Study coordinator: Ray Lee

Conditions Hepatocellular Carcinoma; Gastrointestinal Cancer Metastatic; Neuroendocrine Tumors; Hypoxia; Embolization; Tirapazamine