EGCG for Liver Cancer Prevention

(CATCH-B Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Yujin Hoshida, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: EGCG

Disqualifiers: Severe obesity, Active drinking, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial tests epigallocatechin gallate (EGCG) for its efficacy and safety in preventing development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis.

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

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug EGCG for liver cancer prevention?

Research shows that EGCG, a compound found in green tea, reduced the occurrence of liver tumors in mice and inhibited the growth of liver cancer cells. It also helped prevent liver damage and reduced tumor spread in other types of cancer, suggesting it may be effective in preventing liver cancer. ^{1 2 3 4 5}

Is EGCG safe for human use?

EGCG, found in green tea, is generally safe at doses below 300mg per day, but high doses can cause liver toxicity. Clinical studies show no liver effects at intakes below 600mg per day, but animal studies indicate potential liver damage at higher doses. ^{1 6 7 8 9}

How is the drug EGCG unique for liver cancer prevention?

EGCG, a compound found in green tea, is unique for liver cancer prevention because it can reduce liver inflammation and fibrosis, and inhibit cancer cell growth without harming normal cells. Unlike many traditional treatments, EGCG is taken orally and is well-tolerated, making it a promising non-toxic option for preventing liver cancer. ^{1 2 5 9 10}

Research Team

Yujin Hoshida, MD, PhD

Principal Investigator

UT Southwestern

Eligibility Criteria

This trial is for adults over 18 with liver cirrhosis, a FIB-4 index above 3.25, and no history of liver cancer. They must have good blood, liver, and kidney function and be able to perform daily activities well. All genders and ethnicities are welcome if they don't have the HLA-B*35:01 gene or active worsening of their liver condition.

Inclusion Criteria

My gender or race does not exclude me from this trial.

I am able to care for myself but may not be able to do active work.

FIB-4 index > 3.25

Exclusion Criteria

Active drinking

History of adverse reaction to green tea products

I have used or am using EGCG.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EGCG or placebo for 24 weeks, with potential dose adjustment at week 8 based on biomarker analysis

24 weeks

Monthly visits for adverse event monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including HCC incidence

1 year

Regular follow-up every 6 months

Treatment Details

Interventions

• Epigallocatechin gallate (EGCG) (Cancer Vaccine)

Trial Overview The study is testing EGCG's ability to prevent liver cancer in patients with cirrhosis. Participants will either receive EGCG or a placebo (a substance with no therapeutic effect) to compare outcomes between the two groups.

Participant Groups

Group I: Epigallocatechin gallate 600 - 800mg Experimental Treatment 1 Intervention

Epigallocatechin gallate (EGCG) 600mg will be administered daily via oral route for the initial 12 consecutive weeks on an outpatient basis. The dose of 600 mg will be continued for the second 12 weeks if an interim HCC biomarker test at the end of week 8 improves. If the interim test does not improve without dose-limiting adverse events, the dose will be increased to 800mg for the second 12 weeks, All participants will receive 24 weeks of treatment in total.

Group II: Placebo Placebo Group 1 Intervention

Oral administration of placebo for 24 weeks

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

In a study involving 72 C3H/HeNCrj mice, (-)-epigallocatechin gallate (EGCG) from green tea significantly reduced the incidence of liver tumors (hepatomas) from 83.3% in the control group to 56.0% and 52.2% in the groups receiving 0.05% and 0.1% EGCG, respectively.

EGCG was found to inhibit the growth and secretion of alpha-fetoprotein in human liver cancer cells without affecting their viability, suggesting that it could be a safe and effective preventive agent against liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory effects of (-)-epigallocatechin gallate on spontaneous hepatoma in C3H/HeNCrj mice and human hepatoma-derived PLC/PRF/5 cells. Nishida, H., Omori, M., Fukutomi, Y., et al.[2019]

(-)-Epigallocatechin-3-gallate (EGCG), a compound found in green tea, effectively inhibits the growth of colorectal cancer cells and induces cell death, showing promise as a chemotherapy agent against liver metastases.

In a study involving human colorectal cancer cell lines and SCID mice, EGCG not only reduced liver metastasis without causing weight loss or liver damage but also suppressed blood vessel formation in tumors, indicating its potential safety and efficacy in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer. Maruyama, T., Murata, S., Nakayama, K., et al.[2016]

Epigallocatechin-3-gallate (EGCG) effectively reduces the viability of human hepatocellular carcinoma (HCC) cells, with significant decreases observed at concentrations of 50-400 microg/ml over 48 hours, indicating its potential as a therapeutic agent against liver cancer.

EGCG induces apoptosis in HCC cells by down-regulating the anti-apoptotic proteins COX-2 and Bcl-2, which activates caspase-9 and caspase-3, leading to increased cell death, demonstrating a clear mechanism of action for its anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epigallocatechin-3-gallate induces apoptosis in human hepatocellular carcinoma cells]. Chen, XL., Wang, Q., Cao, LQ., et al.[2013]

Green tea infusions and green tea extract (GTE) products are generally considered safe for consumption, with no association between green tea intake and liver damage in humans, even at doses up to 450mg of EGCG per day.

A proposed tolerable upper intake level of 300mg of EGCG per person per day for food supplements provides a significant safety margin, as clinical studies have shown no liver effects at intakes below 600mg per day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements. Dekant, W., Fujii, K., Shibata, E., et al.[2017]

High doses of the tea polyphenol EGCG (1500 mg/kg) were found to cause significant liver toxicity in male CF-1 mice, leading to a 138-fold increase in plasma alanine aminotransferase (ALT) levels and an 85% reduction in survival rates.

Repeated daily doses of EGCG (750 mg/kg) further exacerbated liver damage, indicating that both the dose and frequency of EGCG administration are critical factors in its hepatotoxic effects, which are linked to oxidative stress and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. Lambert, JD., Kennett, MJ., Sang, S., et al.[2021]

In a study using male Wistar rats with chemically induced liver damage, EGCG (a compound from green tea) was found to be well-tolerated and significantly reduced liver inflammation and tumor formation associated with hepatocellular carcinoma (HCC).

EGCG not only improved liver function markers but also inhibited the progression of fibrosis by affecting specific liver cell types, suggesting its potential as a chemopreventive agent against HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma. Sojoodi, M., Wei, L., Erstad, DJ., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Inhibitory effects of (-)-epigallocatechin gallate on spontaneous hepatoma in C3H/HeNCrj mice and human hepatoma-derived PLC/PRF/5 cells. [2019]

2. Greece pubmed.ncbi.nlm.nih.gov

(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer. [2016]

3. China pubmed.ncbi.nlm.nih.gov

[Epigallocatechin-3-gallate induces apoptosis in human hepatocellular carcinoma cells]. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Epigallocatechin-3-gallate protects against hepatic ischaemia-reperfusion injury by reducing oxidative stress and apoptotic cell death. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3. [2022]

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

Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements. [2017]

7. Canada pubmed.ncbi.nlm.nih.gov

The effect of epigallocatechin gallate on hepatocytes isolated from normal and partially hepatectomized rats. [2014]

8. England pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. [2021]

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

Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma. [2021]

10. Greece pubmed.ncbi.nlm.nih.gov

Epigallocatechin-3-gallate induces the apoptosis of hepatocellular carcinoma LM6 cells but not non-cancerous liver cells. [2014]