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

Primary Purpose

Unresectable Hepatocellular Carcinoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Hepatic artery embolization (HAE)
Bumetanide
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unresectable Hepatocellular Carcinoma focused on measuring Bumetanide, Diuretic, Transarterial Embolization (TAE), 17-141

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (Consent and follow-up only)
  • Memorial Sloan Kettering Monmouth (Consent and follow-up only)
  • Memorial Sloan Kettering Bergen (Consent and follow-up only)
  • Memorial Sloan Kettering Westchester (Consent and follow-up only)
  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bumetanide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 5, 2017
Last Updated
February 7, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03107416
Brief Title
Delivering a Diuretic Into the Liver Artery Followed by Plugging up the Artery to Starve Out Liver Cancer Cells
Official Title
Phase I/II Study of Transarterial Hepatic Embolization With Bumetanide in Unresectable Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 5, 2017 (Actual)
Primary Completion Date
April 5, 2024 (Anticipated)
Study Completion Date
April 5, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable Hepatocellular Carcinoma
Keywords
Bumetanide, Diuretic, Transarterial Embolization (TAE), 17-141

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bumetanide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Hepatic artery embolization (HAE)
Intervention Description
The intervention being studied is HAE for the treatment of HCC in combination with Bumetanide. HAE is a standard of care procedure.
Intervention Type
Drug
Intervention Name(s)
Bumetanide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) (phase I)
Description
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.
Time Frame
1 year
Title
estimate the local tumor progression (LTP) rates (phase II)
Description
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hooman Yarmohammadi, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (Consent and follow-up only)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth (Consent and follow-up only)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen (Consent and follow-up only)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Westchester (Consent and follow-up only)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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