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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03107416

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Unresectable Hepatocellular Carcinoma	Procedure: Hepatic artery embolization (HAE) Drug: Bumetanide	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 5, 2017

Anticipated Primary Completion Date :

Apr 5, 2023

Anticipated Study Completion Date :

Apr 5, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bumetanide 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) The intervention being studied is HAE for the treatment of HCC in combination with Bumetanide. HAE is a standard of care procedure. Drug: Bumetanide 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.

Arm

Intervention/Treatment

Experimental: Bumetanide

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)

The intervention being studied is HAE for the treatment of HCC in combination with Bumetanide. HAE is a standard of care procedure.

Drug: Bumetanide

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.

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge (Consent and follow-up only)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Consent and follow-up only)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Consent and follow-up only)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Westchester (Consent and follow-up only)	Harrison	New York	United States	10604
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065