Diuretic + Arterial Embolization for Liver Cancer

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Child's C cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the water-reducing medication Bumetanide functions in individuals undergoing hepatic artery embolization (HAE) for liver cancer treatment. Researchers aim to determine the safety of Bumetanide at various doses and its impact on treating liver tumors that cannot be surgically removed. The trial seeks participants with liver cancer (HCC) who are already receiving HAE as part of their care, regardless of hepatitis status or previous liver treatments. As a Phase 1/Phase 2 trial, this research focuses on understanding Bumetanide's effects in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that bumetanide, a type of diuretic, helps remove excess fluid from the body. This can benefit conditions like heart failure, liver disease, and kidney disease. Generally, bumetanide is safe for most people, but it can sometimes cause liver-related side effects. These side effects might include changes in liver function tests or a brain condition called encephalopathy, especially in individuals with existing liver problems.

The study under discussion is in its early stages, focusing mainly on safety. Since bumetanide is already used for other health issues, some safety information is available. However, this study specifically examines its safety when combined with a liver cancer treatment called hepatic artery embolization (HAE).

For those considering participation, it's important to know that side effects can vary based on individual health. Always consult a doctor for advice specific to your situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for liver cancer that often rely on chemotherapy or targeted drug therapies, the treatment being investigated here combines a diuretic, bumetanide, with Hepatic Artery Embolization (HAE). Researchers are excited about this approach because bumetanide could potentially enhance the effectiveness of HAE by reducing fluid retention and improving drug delivery to the tumor. Additionally, the use of escalating doses of bumetanide allows for a personalized approach to treatment, which might optimize outcomes for patients. This combination aims to offer a new avenue for controlling liver cancer by directly disrupting the blood supply to tumors while potentially amplifying the treatment's impact with bumetanide.

What evidence suggests that Bumetanide and Hepatic Artery Embolization could be effective for liver cancer?

Research has shown that bumetanide, a medication that helps the body eliminate excess water, might also slow liver cancer growth. In this trial, participants will receive bumetanide, which studies have found can reduce the size and number of liver cancer tumors. Bumetanide achieves this by blocking certain proteins that promote cancer cell growth. Early results suggest that bumetanide effectively slows tumor growth in liver cancer. While typically used to reduce body water, these studies highlight its potential in cancer treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Hooman Yarmohammadi, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with inoperable liver cancer, regardless of viral status. They must have a good performance status (able to carry out daily activities), measurable disease by specific criteria, and be eligible for embolization treatment. People can't join if they're pregnant or breastfeeding, allergic to bumetanide/sulfonamides, have resectable cancer, poor kidney function not on dialysis, certain blood vessel blockages or advanced cirrhosis.

Inclusion Criteria

I am eligible for a procedure to block blood flow to cancer cells.

I have been diagnosed with liver cancer following EASL guidelines.

I have had treatment for my liver before.

Exclusion Criteria

I am at high risk for liver failure after a specific liver procedure due to severe liver disease or extensive liver tumor.

My liver cancer can be surgically removed.

I cannot undergo angiography/embolization due to health issues like severe allergies or poor kidney function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of Bumetanide during transarterial hepatic embolization

1 year

Follow-up

Participants are monitored for local tumor progression and safety after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bumetanide
• Hepatic Artery Embolization (HAE)

Trial Overview The study tests the safety of different doses of Bumetanide when delivered directly into the liver artery followed by plugging up the artery—a procedure known as Hepatic Artery Embolization—to treat liver cancer. The goal is to see how this approach affects patients who are already getting tumor embolization as part of their standard care.

How Is the Trial Designed?

Group I: Bumetanide Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5288206/

Treatment with an SLC12A1 antagonist inhibits tumorigenesis ... Bumetanide reduced the size and number of HCC nodules compared with the Saline group (Figure 5F). The above findings indicated that, as an antagonist of SLC12A ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7558282/

The Anticancer Activity for the Bumetanide-Based Analogs via ... We assessed the potential anticancer activity of bumetanide-based analogues to inhibit the hCA-IX enzymatic activity and cell proliferation of two solid cancer ...

3. oncotarget.com oncotarget.com/article/20240/text/

Discovery of NKCC1 as a potential therapeutic target to ... Bumetanide inhibits HCC growth in vivo​​ This adverse effect might due to the loss of water and electrolytes after using too much bumetanide.

4. researchgate.net researchgate.net/figure/Bumetanide-inhibits-growth-of-SLC12A1-postive-cells-in-vitro-and-in-vivo-A-B-The-effect_fig5_307016305

Bumetanide inhibits growth of SLC12A1-postive cells in ... A study showed that SLC12A5 is upexpressed in colorectal cancer, and could significantly promote xenograft tumor growth and lung metastasis (Xu et al. 2016).

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/osp4.469

Safety and efficacy of pharmacologic weight loss in ... Pharmacologic weight loss in patients with advanced liver fibrosis appears feasible based on preliminary safety and efficacy outcomes in this study.

6. healio.com healio.com/clinical-guidance/drugs/bumetanide

Bumetanide: Uses, Side Effects & Dosage Bumetanide is used to reduce extra fluid in the body (edema) caused by conditions such as heart failure, liver disease, and kidney disease.

7. medcentral.com medcentral.com/drugs/monograph/14575-384051/bumetanide-oral

Bumetanide: uses, dosing, warnings, adverse events, ... Adverse hepatic effects of bumetanide include alteration of liver function test results and encephalopathy (in patients with preexisting hepatic disease).

8. sentinelinitiative.org sentinelinitiative.org/studies/drugs/bumex-bumetanide

Bumex (bumetanide) This study explored whether bumetanide is associated with an increased risk of cancer compared to other loop diuretics and the background ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/bumetanide-oral-route/description/drg-20071274

Bumetanide (oral route) - Side effects & dosage Bumetanide is given to help treat fluid retention (edema) and swelling that is caused by congestive heart failure, liver disease, kidney disease, or other ...

10. pdf.hres.ca pdf.hres.ca/dpd_pm/00066784.PDF

BURINEX® (bumetanide) Product Monograph, version 7.0 The safety profile of BURINEX has not been established in the pediatric population. 8.6 Post-Market Adverse Reactions. Blood and lymphatic ...