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

• ClinicalTrials.gov Identifier: NCT03107416
• Recruitment Status: Active, not recruiting
• First Posted: April 11, 2017
• Last Update Posted: February 8, 2023
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

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 (Clinical Trial)
• 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: April 5, 2017
• Estimated Primary Completion Date: April 5, 2024
• Estimated Study Completion Date: April 5, 2024

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.

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose (MTD) (phase I) [ Time Frame: 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.
2. estimate the local tumor progression (LTP) rates (phase II) [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New Jersey

Memorial Sloan Kettering Basking Ridge (Consent and follow-up only)

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Monmouth (Consent and follow-up only)

Middletown, New Jersey, United States, 07748

Memorial Sloan Kettering Bergen (Consent and follow-up only)

Montvale, New Jersey, United States, 07645

United States, New York

Memorial Sloan Kettering Westchester (Consent and follow-up only)

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Hooman Yarmohammadi, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT03107416
• Other Study ID Numbers: 17-141
• First Posted: April 11, 2017
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

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

Keywords provided by Memorial Sloan Kettering Cancer Center:

Bumetanide; Diuretic; Transarterial Embolization (TAE); 17-141

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Bumetanide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action