TACE + Durvalumab + Bevacizumab for Liver Cancer

(EMERALD-1 Trial)

Recruiting at 155 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: Cardiovascular disease, Coagulopathy, GI bleeding, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 5 years

724 Participants Needed

Trial Summary

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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment TACE + Durvalumab + Bevacizumab for liver cancer?

Research shows that combining transarterial chemoembolization (TACE) with drugs like atezolizumab and bevacizumab has improved outcomes in liver cancer patients. Bevacizumab, when used with other cancer drugs, has been shown to improve survival in various advanced cancers, suggesting potential benefits in liver cancer treatment. ^{1 2 3 4 5}

What is the safety profile of Bevacizumab (Avastin) in humans?

Bevacizumab (Avastin) is generally safe for humans, with common side effects including high blood pressure, protein in urine, and minor bleeding, which are usually manageable. Rare but serious side effects can include wound healing issues, gastrointestinal perforations, and blood clots. ^{4 6 7 8 9}

What makes the TACE + Durvalumab + Bevacizumab treatment unique for liver cancer?

This treatment combines transarterial chemoembolization (TACE), which directly targets liver tumors, with durvalumab, an immunotherapy drug that helps the immune system fight cancer, and bevacizumab, which inhibits blood vessel growth in tumors. This combination is unique because it integrates different mechanisms to potentially enhance treatment effectiveness for liver cancer. ^{1 2 3 10 11}

What is the purpose of this trial?

A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab and bevacizumab therapy in patients with locoregional hepatocellular carcinoma

Research Team

Bruno Sangro, MD

Principal Investigator

Clinica Universidad de Navarra

Riccardo Lencioni, MD FSIR EBIR

Principal Investigator

University of Pisa / Miami Cancer Institute

Eligibility Criteria

This trial is for adults with hepatocellular carcinoma (a type of liver cancer) that hasn't spread outside the liver and can't be treated with surgery or transplantation. Participants should have a certain level of liver function (Child-Pugh score class A to B7), an ECOG performance status of 0 or 1, and no recent significant cardiovascular issues, GI perforations, bleeding disorders, or major surgeries.

Inclusion Criteria

My organs and bone marrow are working well.

My condition cannot be cured with surgery or transplantation, but can be treated with TACE.

Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria

Exclusion Criteria

I have a history of kidney disorders.

Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded

I haven't had surgery in the last 28 days and don't have bleeding disorders.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transarterial chemoembolization (TACE) in combination with either durvalumab monotherapy or durvalumab plus bevacizumab therapy

Approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 years

Treatment Details

Interventions

• Bevacizumab
• Durvalumab
• Transarterial Chemoembolization (TACE)

Trial Overview The study tests if combining TACE—a procedure blocking blood flow to parts of the liver—with Durvalumab and Bevacizumab drugs improves outcomes in patients with localized liver cancer. Some participants will receive a placebo instead of these drugs as part of the study's comparison.

Participant Groups

Group I: Arm B Experimental Treatment 3 Interventions

Transarterial Chemoembolization (TACE) in combination with Durvalumab and Bevacizumab

Group II: Arm A Experimental Treatment 3 Interventions

Transarterial Chemoembolization (TACE) in combination with Durvalumab

Group III: Arm C Placebo Group 2 Interventions

Transarterial Chemoembolization (TACE) in combination with Placebos

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study of 139 patients with advanced hepatocellular carcinoma, the combination of transarterial chemoembolization (TACE) with atezolizumab and bevacizumab (TACE-Atez/Bev) resulted in a significantly higher objective response rate (38.7%) compared to atezolizumab and bevacizumab alone (16.9%).

TACE-Atez/Bev also demonstrated improved overall survival (14 months vs. 10 months) and progression-free survival (10 months vs. 6 months) compared to the Atez/Bev group, indicating it may be a more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study. Cao, F., Shi, C., Zhang, G., et al.[2023]

Bevacizumab (Avastin) has been shown to improve progression-free and overall survival in patients with various advanced cancers, including colorectal, lung, renal, breast, and ovarian cancers, based on phase III trials and real-world studies.

The safety profile of bevacizumab is well established, with manageable adverse effects such as hypertension and proteinuria, making it a valuable treatment option for patients with advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab: a review of its use in advanced cancer. Keating, GM.[2022]

Atezolizumab combined with bevacizumab is the first approved immunotherapy for first-line treatment of unresectable hepatocellular carcinoma (HCC), showing promising efficacy and tolerability in over 80 countries.

The DEMAND study is the first phase II trial to investigate the safety and efficacy of this combination therapy in patients with intermediate-stage HCC undergoing transarterial chemoembolization (TACE), focusing on 24-month survival rates and other important health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol. Ben Khaled, N., Seidensticker, M., Ricke, J., et al.[2022]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

The DEDUCTIVE trial is a phase Ib study evaluating the safety and tolerability of combining durvalumab, a PD-L1 inhibitor, with tivozanib, a VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC).

Both durvalumab and tivozanib have shown effectiveness as single agents in HCC, but this trial aims to explore their concurrent use, particularly in treatment-naive patients and those who have progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). Mahmood, S., Li, D., Lee, A., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Transarterial chemoembolization combined donafenib with/without PD-1 for unresectable HCC in a multicenter retrospective study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study. [2023]

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

Sorafenib combined with transarterial chemoembolization in patients with hepatocellular carcinoma: a meta-analysis and systematic review. [2022]

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

Bevacizumab: a review of its use in advanced cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Atezolizumab and bevacizumab with transarterial chemoembolization in hepatocellular carcinoma: the DEMAND trial protocol. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. [2015]

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

Bevacizumab: a review of its use in combination with paclitaxel or capecitabine as first-line therapy for HER2-negative metastatic breast cancer. [2021]

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

Bevacizumab: in first-line treatment of metastatic breast cancer. [2018]

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

Cutaneous lupus erythematosus in a patient undergoing intravitreal bevacizumab injections: case report and review of the literature. [2022]

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

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab or Lenvatinib for Unresectable Hepatocellular Carcinoma: A Propensity Score Matched Study. [2023]

11. England pubmed.ncbi.nlm.nih.gov

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). [2023]