Chemoembolization for Liver Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Carin Gonsalves, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Thomas Jefferson University

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial studies a treatment that injects chemotherapy and blocking agents into the liver's blood vessels to target tumors in patients with eye cancer that has spread to the liver. The goal is to cut off the tumor's blood supply and apply chemotherapy directly, helping to shrink or eliminate the tumors. This method delivers highly concentrated drugs to the tumor and stops blood flow to it.

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.

What data supports the idea that Chemoembolization for Liver Cancer is an effective treatment?

The available research shows that transarterial chemoembolization (TACE) is associated with better survival for patients with a specific type of liver cancer called BCLC-stage B hepatocellular carcinoma. However, the evidence is mixed when comparing TACE to other treatments like liver resection or radiofrequency ablation. Some studies suggest TACE is beneficial, while others find it controversial or unclear. Overall, TACE seems to help certain patients, but its effectiveness can vary depending on the patient's condition and the stage of cancer. ^{1 2 3 4 5}

What safety data is available for chemoembolization in liver cancer treatment?

Safety data for chemoembolization, specifically Transarterial Chemoembolization (TACE), shows that it is generally a safe procedure with some adverse events. Studies indicate that adverse events can include nausea, vomiting, and moderate transient epigastric pain. Severe adverse events like thrombocytopenia are rare. Comparisons between conventional TACE and drug-eluting bead TACE (DEB-TACE) suggest differences in adverse event profiles, but both are considered safe. Biliary complications are rare but possible. Overall, TACE is a safe and effective palliative treatment for unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC). ^{6 7 8 9 10}

Is the treatment Transarterial Chemoembolization (TACE) with the drug Carmustine promising for liver cancer?

Transarterial Chemoembolization (TACE) is a treatment often used for liver cancer, especially in certain stages. It is considered a standard procedure and is sometimes used in place of other treatments. However, the research does not specifically mention Carmustine, so it's unclear if TACE with Carmustine is promising based on the provided information. ^{1 5 11 12 13}

Research Team

Carin Gonsalves, MD

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

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.

Treatment Details

Interventions

• Carmustine (Alkylating agents)
• Transarterial Chemoembolization (Procedure)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Eugene Kennedy

Thomas Jefferson University

Chief Medical Officer since 2020

MD

Dr. Joseph G. Cacchione

Thomas Jefferson University

Chief Executive Officer since 2022

MD, MBA

Findings from Research

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]

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]

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]

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]

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]

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 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 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 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]

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 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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of transcatheter arterial chemoemboliazation in the real-life management of unresectable hepatocellular carcinoma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Liver resection versus transarterial chemoembolization for the initial treatment of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Transarterial chemoembolization as a substitute to radiofrequency ablation for treating Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. [2022]

7. United States 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. [2022]

8. New Zealand 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Treatment of Huge Hepatocellular Carcinoma Using Cinobufacini Injection in Transarterial Chemoembolization: A Retrospective Study. [2020]

10. France pubmed.ncbi.nlm.nih.gov

Biliary complications of arterial chemoembolization of hepatocellular carcinoma. [2015]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Transarterial chemoembolisation for breast cancer with liver metastasis: A systematic review. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

Treatment outcome of patients with liver-only metastases from breast cancer after mastectomy: a retrospective analysis. [2021]

13. United States 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. [2022]