Unresectable Hepatocellular Carcinoma
Conditions
Keywords
Bumetanide, Diuretic, Transarterial Embolization (TAE), 17-141
Brief summary
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.
Interventions
PROCEDUREHepatic artery embolization (HAE)
The intervention being studied is HAE for the treatment of HCC in combination with Bumetanide. HAE is a standard of care procedure.
DRUGBumetanide
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.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) (phase I) | 1 year | 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. |
| estimate the local tumor progression (LTP) rates (phase II) | 1 year | 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. |
Countries
United States
Outcome results
None listed