Delivering a Diuretic Into the Liver Artery Followed by Plugging up the Artery to Starve Out Liver Cancer Cells

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of Bumetanide , at different doses to find out what effects, if any, it has on people who undergo tumor TAE as part of their regular care. Bumetanide is a commonly used medication to reduce the amount of water in the body.

Official Title
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Phase I/II Study of Transarterial Hepatic Embolization With Bumetanide in Unresectable Hepatocellular Carcinoma

Conditions
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Unresectable Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: Hepatic artery embolization (HAE)
* Drug: Bumetanide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with diagnoses of HCC according to European Association for the Study of Liver disease (EASL) criteria for diagnosis (See Appendix 1). Regional lymphadenopathy will be allowed. Any virus status accepted (e.g. Hepatitis C etc.) Any prior liver treatment Patients within unresectable HCC At least 18 years old ECOG performance status 0 or 1 Radiographically measurable disease per mRECIST 1.1 Meets standard of care to undergo embolization Exclusion Criteria: Women who are pregnant or lactating Documented hypersensitivity to bumetanide or sulfonamides Patients with resectable HCC High risk for post-embolization hepatic failure: °Child's C cirrhosis °> 80% liver involvement by tumor Contraindication to angiography/embolization including: Patients cannot receive contrast: Severe allergic reaction to contrast despite premedication Poor renal function not on dialysis Other, based on judgment of the investigator ECOG score 2 Main portal vein tumor thrombus BCLC D = patients with distant metastasis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bumetanide<br>Three escalating doses of bumetanide will be used: 0.01 mg/kg (level 1), 0.02 mg/kg (level 2) and 0.04 mg/kg (level 3) in a standard 3+3 design. Starting with level 1, three patients will first be enrolled at each level. | Procedure: Hepatic artery embolization (HAE)<br>* The intervention being studied is HAE for the treatment of HCC in combination with Bumetanide. HAE is a standard of care procedure.<br>Drug: Bumetanide<br>* Intra-arterial (IA) injection of 0.01mg/kg of Bumetanide in the first cohort, 0.02 mg/kg in the second cohort and 0.04 mg/kg of IA Bumetanide in the final cohort patients during standard HAE until stasis is evident.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) (phase I) | Three escalating doses of bumetanide will be used: 0.01 mg/kg (level 1), 0.02 mg/kg (level 2) and 0.04 mg/kg (level 3) in a standard 3+3 design. Starting with level 1, three patients will first be enrolled at each level. | 1 year | 
| estimate the local tumor progression (LTP) rates (phase II) | After the last first stage patient has three months followup, 6-month LTP will be estimated using Kaplan-Meier methods. If the one-sided 90% lower confidence bound is less than 40% the study will stop. Otherwise 12 more patients will be enrolled for a total of 30. At the end of the study 12-month LTP will be estimated using competing risk (cumulative incidence) methods. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bumetanide, Diuretic, Transarterial Embolization (TAE), 17-141