TACE + Durvalumab + Bevacizumab for Liver Cancer

(EMERALD-1 Trial)

Not currently recruiting at 193 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for liver cancer that remains confined to the liver and cannot be treated with surgery or transplantation. The study evaluates the effectiveness of transarterial chemoembolization (TACE), a method that delivers chemotherapy directly to the liver, in combination with the drugs durvalumab (an immunotherapy drug) and bevacizumab (also known as Avastin, an anti-angiogenesis drug). Participants will join one of three groups: TACE with durvalumab, TACE with both durvalumab and bevacizumab, or TACE with placebos (inactive substances). Individuals with liver cancer limited to the liver and in generally good health may qualify for participation. As a Phase 3 trial, this study serves as the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

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

Research has shown that the combination of transarterial chemoembolization (TACE) and durvalumab is generally well-tolerated. A study on this combination for advanced bile duct cancer found it safe, with manageable side effects. Common issues included fatigue and minor liver problems, which were not severe for most patients.

For the combination of TACE, durvalumab, and bevacizumab, safety data is also encouraging. Another study found that adding these drugs to TACE resulted in side effects similar to the TACE-durvalumab combination. Patients experienced minor issues like fatigue and some liver-related effects, but these were usually not serious.

Both combinations indicate that side effects are present but generally not overwhelming. Understanding these possible effects can help prospective trial participants make informed decisions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine innovative immunotherapy with traditional methods. Unlike standard treatments like sorafenib, which primarily target cancer cells directly, this approach uses durvalumab, an immunotherapy drug, to harness the body's immune system to fight cancer. Bevacizumab, another key component, inhibits blood vessel growth that tumors need to thrive. Additionally, transarterial chemoembolization (TACE) delivers chemotherapy directly to the liver tumor, effectively cutting off its blood supply. These combined mechanisms offer a multifaceted attack on liver cancer, providing hope for improved outcomes compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that combining transarterial chemoembolization (TACE) with durvalumab and bevacizumab may effectively treat liver cancer. In this trial, participants in Arm B will receive TACE with both durvalumab and bevacizumab. One study found that this combination reduced the risk of cancer progression or death by 23% compared to TACE alone. Another study found that patients experienced a longer period without cancer worsening. These findings suggest that adding durvalumab and bevacizumab to TACE might help slow liver cancer. Participants in Arm A will receive TACE with durvalumab, while Arm C will involve TACE with placebos. ^{6 7 8 9 10}

Who Is on the Research Team?

Bruno Sangro, MD

Principal Investigator

Clinica Universidad de Navarra

Riccardo Lencioni, MD FSIR EBIR

Principal Investigator

University of Pisa / Miami Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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) 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]

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) 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.575

Outcomes by transarterial chemoembolization (TACE) ... Results: Overall, 59.3% of pts received cTACE and 40.7% received DEB-TACE in the D + B + TACE arm; similarly, 58.5% of pts received cTACE and ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)02551-0/abstract

Durvalumab with or without bevacizumab with transarterial ... As of data cutoff (Sept 11, 2023) median follow-up for progression-free survival was 27·9 months (95% CI 27·4–30·4), median progression-free ...

3. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2024/imfinzi-with-tace-and-bevacizumab-in-patients-with-hepatocellular-carcinoma-eligible-for-embolisation.html

Imfinzi plus transarterial chemoembolisation (TACE) and ... Treatment with Imfinzi plus TACE and bevacizumab reduced the risk of disease progression or death by 23% compared to TACE alone.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)00314-4/fulltext

166P Outcomes by baseline liver function in EMERALD-1: ... Conclusions. These results support a favourable risk-benefit profile with D + B + TACE in embolisation-eligible uHCC regardless of baseline ALBI gr.

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/imfinzi-durvalumab-plus-transarterial-chemoembolization-tace-and-bevacizumab-reduced-the-risk-of-disease-progression-or-death-by-23-vs-tace-in-liver-cancer-eligible-for-embolization-01192024.html

IMFINZI® (durvalumab) plus transarterial ... Adding durvalumab and bevacizumab to TACE reduced the risk of disease progression or death by twenty-three per cent for patients with liver ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06911255

NCT06911255 | Safety and Efficacy of Tremelimumab ... The purpose of this clinical trial is to evaluate the safety and efficacy of tremelimumab + durvalumab administered concurrently with transarterial ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12233867/

Clinical outcomes of transarterial chemoembolization ... This study aimed to evaluate the safety and efficacy of TACE combined with durvalumab for treating advanced and metastatic BTC.

8. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D933GC00001

A global study to evaluate transarterial chemoembolization ... A randomized, double-blind, placebo-controlled, multicenter, global Phase III study to determine the efficacy and safety of transarterial chemoembolization ( ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04988945

Study Details | NCT04988945 | TACE and SBRT Followed ... Combined TACE+SBRT is a more potent local therapy than TACE in preventing tumor progression, and it may potentially translate into survival benefit.

10. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03638141/

Clinical Trial: NCT03638141 The purpose of this study is to determine the safety and efficacy of immunotherapy durvalumab and tremelimumab combined with DEB-TACE in patients with ...