Chemoembolization for Liver Cancer

Overseen By Carin Gonsalves, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Must not be taking: Immune check-point inhibitors

Disqualifiers: Liver-directed treatments, Hypertension, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Variable (4-7 weeks per cycle)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for liver cancer originating from a specific eye cancer called uveal melanoma. The treatment delivers chemotherapy directly to the liver to shrink or eliminate tumors. This method, known as Transarterial Chemoembolization (TACE), specifically targets liver tumors. Individuals with uveal melanoma that has spread to the liver and who have not previously received liver-directed therapies might be suitable candidates. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, immune check-point inhibitors are not allowed while on the study, and certain conditions like active viral or autoimmune hepatitis requiring treatment may affect eligibility. It's best to discuss your specific medications with the trial team.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, immune check-point inhibitors are not allowed during the study, and certain treatments for extrahepatic metastases are permitted. It's best to discuss your specific medications with the trial team.

What prior data suggests that transarterial chemoembolization is safe for treating liver metastases?

Research has shown that the treatment under study, using transarterial chemoembolization (TACE) with the drug carmustine, demonstrated promising safety results in earlier studies. In a study with 20 patients, a similar method using TACE with other drugs proved effective and had a low rate of serious side effects, indicating that severe side effects were uncommon and suggesting it could be well-tolerated.

While specific data on using carmustine with TACE for uveal melanoma liver metastases remain limited, TACE has been studied for treating liver conditions in general. These studies often find that TACE is a focused way to treat liver tumors, with side effects that are usually manageable.

This clinical trial is in its second phase, indicating that earlier tests on humans have already suggested it is likely safe. This phase focuses more on assessing the treatment's effectiveness while still monitoring safety. So far, the treatment appears safe, but the trial will continue to monitor for any possible risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for liver cancer because it combines carmustine with transarterial chemoembolization (TACE), offering a novel approach compared to standard treatments like systemic chemotherapy or surgical resection. This treatment delivers carmustine directly into the liver tumor via the hepatic artery, using ethiodized oil to help localize and retain the drug, while a gelatin sponge blocks blood flow, enhancing the drug's effect. This targeted delivery method aims to maximize the tumor's exposure to the chemotherapy while minimizing systemic side effects, potentially offering more effective and safer treatment options for patients with liver cancer.

What evidence suggests that transarterial chemoembolization is effective for liver metastases?

Research has shown that transarterial chemoembolization (TACE), the treatment participants in this trial will receive, can be effective for liver tumors. This treatment delivers chemotherapy directly to the liver, targeting cancer cells more precisely. In this trial, the chemotherapy drug used is carmustine, which kills or stops the growth of these cancer cells. Studies have found that TACE can shrink tumors or even make them disappear in some patients with liver metastases. While most research focuses on liver cancers like hepatocellular carcinoma, this method also shows promise for other liver metastases, including those from uveal melanoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Carin Gonsalves, MD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for adults with uveal melanoma that has spread to the liver. Participants must be able to consent, have good kidney function and physical health, a certain level of blood cells and albumin, and tumors detectable by imaging. They can't join if they're under 18, pregnant or breastfeeding, have had certain previous liver treatments or surgeries, uncontrolled other diseases like heart failure or hepatitis, severe bleeding tendencies or life-threatening allergies to specific drugs.

Inclusion Criteria

Your albumin level is 3.0 grams per deciliter or higher.

Your bilirubin level needs to be below 2.0 mg/ml, unless you have Gilbert's Syndrome, in which case a level below 3.0 mg/ml is allowed.

My cancer, which started in the eye, has spread to my liver.

Exclusion Criteria

My brain metastases are stable for over 4 weeks after treatment.

I need treatment soon for cancer spread beyond the liver, but I can have radiation.

I have had treatments targeting my liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo transarterial chemoembolization (TACE) with carmustine, ethiodized oil, and gelatin sponge. Treatment repeats every 4 weeks for bilobar disease or every 7 weeks for unilobar disease.

Variable (4-7 weeks per cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 2 months for up to 2 years.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carmustine
• Transarterial Chemoembolization

Trial Overview The study tests transarterial chemoembolization on liver metastases from uveal melanoma. It involves injecting carmustine (chemotherapy) combined with ethiodized oil and gelatin sponge directly into the liver artery to shrink or eliminate tumors.

How Is the Trial Designed?

Group I: Treatment (carmustine, ethiodized oil, gelatin sponge) Experimental Treatment 4 Interventions

Patients undergo TACE by receiving an infusion of carmustine dissolved in ethiodized oil and an injection of gelatin sponge. Treatment repeats Q4W for bilobar disease or Q7W for unilobar disease in the absence of disease progression or unacceptable toxicity or until maximum clinical benefit is obtained.

Carmustine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as BiCNU for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Approved in European Union as Carmubris for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Approved in Canada as BCNU for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Published Research Related to This Trial

In a study of 168 patients with hepatocellular carcinoma who underwent 305 transarterial chemoembolization (TACE) procedures, biliary complications occurred in only 3.6% of patients, indicating that such complications are infrequent.

The types of biliary complications included minimal intrahepatic biliary dilatation, biliary stricture, and intrahepatic biloma, with treatment varying based on severity, highlighting the importance of clinical suspicion and imaging for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biliary complications of arterial chemoembolization of hepatocellular carcinoma. Dhamija, E., Paul, SB., Gamanagatti, SR., et al.[2015]

In a study of 246 HCC patients undergoing 267 procedures, conventional transarterial chemoembolization (cTACE) was associated with the highest incidence of adverse events (AEs) at 86.2%, compared to 76.6% for drug-eluting bead TACE (DEB-TACE) and 63.3% for radiofrequency ablation (RFA).

Specific adverse events like fatigue and nausea were more common in the cTACE group, indicating that RFA may be a safer option for patients due to its lower overall AE incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of Adverse Events Among Radiofrequency Ablation, Conventional Transarterial Chemoembolization (TACE) and Drug-Eluting Bead TACE in Treating Hepatocellular Carcinoma Patients. Cao, G., Liu, Y., Li, L., et al.[2022]

In a study of 242 patients with BCLC stage 0/A hepatocellular carcinoma, transarterial chemoembolization (TACE) was found to have a higher local recurrence rate compared to radiofrequency ablation (RFA), indicating a potential limitation in TACE's effectiveness for this patient group.

Despite the higher recurrence rate, the overall survival rates for patients treated with TACE were comparable to those treated with RFA, suggesting that TACE can be a viable alternative treatment option for certain patients with early-stage liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transarterial chemoembolization as a substitute to radiofrequency ablation for treating Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma. Ishikawa, K., Chiba, T., Ooka, Y., et al.[2022]

Transarterial chemoembolisation (TACE) has been shown to be an effective treatment for patients with breast cancer liver metastasis (BCLM), with median overall survival ranging from 7.3 to 47.0 months across 10 studies involving 519 patients.

While TACE is effective, it can cause significant side effects, with Grade 3 and 4 toxicities reported in up to 17.4% of patients, highlighting the need for careful patient selection and multidisciplinary team discussions before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transarterial chemoembolisation for breast cancer with liver metastasis: A systematic review. Wang, M., Zhang, J., Ji, S., et al.[2018]

In a study of 38 patients with resectable BCLC stage B hepatocellular carcinoma (HCC), elevated levels of α-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) were identified as significant predictors of micrometastases and poor survival outcomes after surgical resection.

Validation in a separate group of 54 patients undergoing transarterial chemoembolization (TACE) showed that those with AFP <110 and PIVKA-II <800 had significantly better survival rates, suggesting these biomarkers can help identify patients who would benefit most from surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma. Suh, SW., Choi, YS.[2018]

In a study of 51 patients with unresectable hepatocellular carcinoma, TACE using multiple anticancer drugs did not show a significant improvement in radiographic response or progression-free survival compared to TACE using epirubicin alone.

However, the multi-drug TACE group experienced significantly more severe liver enzyme elevation and hepatic artery abnormalities, indicating potential safety concerns with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of transcatheter arterial chemoembolization (TACE) with multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluorouracil) compared with TACE with epirubicin for treatment of hepatocellular carcinoma. Sahara, S., Kawai, N., Sato, M., et al.[2022]

A meta-analysis of 4 randomized controlled trials showed that combining transarterial chemoembolization (TACE) with percutaneous ablation significantly reduces mortality in patients with hepatocellular carcinoma (HCC), regardless of tumor size.

Transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) after liver surgery improves survival and reduces tumor recurrence, highlighting the benefits of a multimodal treatment approach for HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Marelli, L., Stigliano, R., Triantos, C., et al.[2014]

The study evaluated the safety and efficacy of degradable starch microspheres (DSM) as an embolic agent in transarterial chemoembolization (TACE) for intrahepatic cholangiocellular carcinoma (ICC), involving 25 procedures across seven patients, showing that DSM-TACE is generally safe with manageable adverse events.

While the objective response rate was low at 12%, disease control was achieved in 44% of treatments, indicating that DSM can be effective in managing ICC, though further studies are needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Degradable Starch Microspheres Transcatheter Arterial Chemoembolization (DSM-TACE) in Intrahepatic Cholangiocellular Carcinoma (ICC): Results from a National Multi-Center Study on Safety and Efficacy. Schicho, A., Pereira, PL., Pützler, M., et al.[2022]

In a study of 208 patients treated with drug-eluting beads transarterial chemoembolisation (DEB-TACE), liver or biliary injuries occurred in 30.8% of patients, with a significant association found between these injuries and the use of DEB-TACE, regardless of the type of tumor.

The most serious injury, biloma or liver infarct, was particularly linked to DEB-TACE and non-cirrhotic endocrine tumors, suggesting that DEB-TACE may pose higher risks in non-cirrhotic livers compared to cirrhotic livers, which may have protective mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. Guiu, B., Deschamps, F., Aho, S., et al.[2022]

In a study of 56 patients with large hepatocellular carcinoma (HCC), Cinobufacini injection showed a significantly higher objective response rate (53.6%) compared to epirubicin (23.1%) during transarterial chemoembolization (TACE).

While both treatments had similar median survival times and progression times, the Cinobufacini group experienced fewer adverse events, indicating it may be a safer option for patients undergoing TACE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Huge Hepatocellular Carcinoma Using Cinobufacini Injection in Transarterial Chemoembolization: A Retrospective Study. Dong, J., Zhai, X., Chen, Z., et al.[2020]

In a study of 87 patients, those receiving combined treatment of transcatheter arterial chemoembolization (TACE) and systemic chemotherapy (TSC) had a significantly higher response rate of 59.1% compared to 34.9% for those receiving only systemic chemotherapy (SC).

The TSC group also showed improved survival rates at 1, 2, and 3 years (76.2%, 66.7%, and 47.6%, respectively) compared to the SC group (48.1%, 29.6%, and 7.4%), suggesting that TACE combined with systemic chemotherapy may enhance survival for patients with liver metastases from breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcome of patients with liver-only metastases from breast cancer after mastectomy: a retrospective analysis. Duan, XF., Dong, NN., Zhang, T., et al.[2021]

Trans-arterial chemoembolization (TACE) is a safe and effective treatment for patients with unresectable hepatocellular carcinoma (HCC), showing a 1-year survival rate of 73.2% and a low procedure-related mortality of 1.4% based on a study of 71 patients over an average follow-up of 24.6 months.

Factors such as tumor size, Child-Pugh classification, alcohol abuse, and tumor response significantly influence survival outcomes, with patients diagnosed during surveillance having better survival rates compared to those diagnosed after symptoms developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of transcatheter arterial chemoemboliazation in the real-life management of unresectable hepatocellular carcinoma. Mazioti, A., Gatselis, NK., Rountas, C., et al.[2021]

Liver resection (LR) significantly improves overall survival rates compared to transarterial chemoembolization (TACE) in patients with Barcelona Clinic Liver Cancer (BCLC)-B hepatocellular carcinoma, based on an analysis of 11 studies involving 3366 patients.

While LR offers better survival outcomes, it also comes with a higher risk of treatment-related mortality and infections compared to TACE, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver resection versus transarterial chemoembolization for the initial treatment of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma. Yang, B., Zheng, B., Yang, M., et al.[2019]

Citations

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Transarterial Chemoembolization for Hepatocellular ... In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10940046/

Chemoembolization Beyond Hepatocellular Carcinoma Overall, data regarding cTACE for colorectal liver metastases demonstrate that cTACE is feasible and similarly effective with different chemotherapy emulsion ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4099-x

Transarterial chemoembolization (TACE) using mitomycin and ... The aim of this retrospective study was to compare tumor response and survival time after transarterial chemoembolization in HCC patients.

4. blueshieldca.com blueshieldca.com/content/dam/bsca/en/provider/docs/2023/August/PRV_TACE_LvrMets.pdf

8.01.11 Transcatheter Arterial Chemoembolization to Treat ... Adverse Events. Transcatheter arterial chemoembolization of the liver has been associated with potentially life- threatening toxicities and complications, ...

5. researchgate.net researchgate.net/publication/6694756_Transarterial_Therapy_for_Hepatocellular_Carcinoma_Which_Technique_Is_More_Effective_A_Systematic_Review_of_Cohort_and_Randomized_Studies

(PDF) Transarterial Therapy for Hepatocellular Carcinoma The post-TACE complications were: acute liver failure, 7.5% (range 0-49%); acute renal failure, 1.8% (0-13%); encephalopathy, 1.8% (0-16%); ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11098243/

A study of 20 cases - PMC TACE, camrelizumab, and donafenib combination therapy in Chinese advanced HCC patients show effectiveness in extending survival with low severe AEs incidence.

7. iv.iiarjournals.org iv.iiarjournals.org/content/23/1/131

Intra-arterial Hepatic Chemoembolization (TACE) of Liver ... If metastases appear, none of the systemic treatments established for cutaneous melanoma so far have any significant impact. Several authors have adopted trans- ...

8. d-nb.info d-nb.info/1155660064/34

Transarterial chemoembolization (TACE) using mitomycin ... Our data suggest a slight benefit of the use of lipiodol and DSM in comparison of using lipiodol only for chemoembolization of HCC in terms of local tumor.