TARE + Durvalumab + Bevacizumab for Liver Cancer

(EMERALD-Y90 Trial)

Recruiting at 18 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Disqualifiers: Curative surgery, HBV and HDV, Cardiovascular, Hypertension, Thrombotic event, 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

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

Compensation: Varies

Number of Visits: 2

Duration: Approximately 3 years

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with liver cancer that cannot be surgically removed. It combines two drugs, durvalumab and bevacizumab, administered after a procedure called TARE (Transarterial Radioembolization), which uses tiny radioactive beads to target cancer cells. The trial aims to assess the safety and effectiveness of this combination in treating liver cancer. Individuals with liver cancer confined to the liver and unsuitable for surgery might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if 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 shows that both durvalumab and bevacizumab have undergone safety testing in humans. Durvalumab is generally well-tolerated and has FDA approval for other cancers, such as bladder cancer. Side effects can include tiredness, skin rash, and decreased appetite, but these are often manageable.

Bevacizumab also has approval for treating various cancers, including colorectal and lung cancer. Common side effects might include high blood pressure and protein in the urine, which doctors usually monitor and control.

Transarterial radioembolization (TARE) using Yttrium 90 glass microspheres has been used for liver cancer. It is generally well-tolerated but can sometimes cause fatigue, nausea, or pain in the liver area.

Since this trial is in Phase 2, earlier studies showed some safety, but more data is needed for confirmation. Researchers will closely monitor participants to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for liver cancer, which typically involves surgery, chemotherapy, or targeted therapy, this treatment combines Yttrium 90 glass microspheres with Durvalumab and Bevacizumab. This approach is unique because it uses transarterial radioembolization (TARE) to deliver radiation directly to the tumor, minimizing damage to surrounding healthy tissue. Additionally, Durvalumab and Bevacizumab are immunotherapeutic agents; Durvalumab helps the immune system recognize and attack cancer cells, while Bevacizumab cuts off the tumor's blood supply. Researchers are excited about this combination because it not only targets the cancer directly but also harnesses the body’s own immune system for a potentially more effective attack.

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

Research has shown that combining TARE (a treatment that delivers radiation directly to the liver) with the drugs Durvalumab and Bevacizumab may help treat liver cancer that cannot be removed by surgery. In this trial, participants will receive this combination therapy. Durvalumab enhances the immune system's ability to find and attack cancer cells, while Bevacizumab stops the blood supply that tumors need to grow. Patients who have received similar treatments have demonstrated better results in controlling liver cancer. These treatments aim to shrink tumors and prevent their spread. While more research is needed, this combination therapy is based on strong scientific evidence and early positive results. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with unresectable liver cancer (HCC) who can undergo TARE, have a Child-Pugh score class A (indicating good liver function), no cancer outside the liver, at least one measurable tumor in the liver, and are generally in good health or only mildly ill. They must also meet specific criteria for lung safety during treatment and have enough healthy liver tissue.

Inclusion Criteria

My liver function is mildly affected.

I have a measurable tumor and am eligible for a specific radiation therapy.

My liver cancer cannot be removed with surgery.

Exclusion Criteria

I have not had a heart attack, stroke, or similar event in the last 6 months.

I have had treatment for liver cancer that couldn't be removed by surgery.

I haven't had any major stomach or intestine issues, like bleeding or unhealed ulcers, in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Transarterial Radioembolization (TARE)

Participants undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation

1 day

1 visit (in-person)

Treatment

Participants receive durvalumab monotherapy followed by durvalumab + bevacizumab

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose of study drug

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Durvalumab
• Transarterial Radioembolization (TARE)

Trial Overview The study tests if combining Durvalumab (an IV drug) and Bevacizumab (another IV drug) after Transarterial Radioembolization (TARE using Yttrium 90 microspheres) improves outcomes for patients with HCC that cannot be surgically removed. The effectiveness and safety of this combination therapy are being evaluated.

How Is the Trial Designed?

Group I: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab Experimental Treatment 3 Interventions

Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.

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

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

In a study of six patients with unresectable colorectal cancer treated with bevacizumab, the combination chemotherapy was well-tolerated, with most adverse drug reactions being grade 2 or less.

Only one patient experienced grade 3 neutropenia, and there were no specific adverse effects directly related to bevacizumab, suggesting it can be safely used in combination with chemotherapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer]. Fujimoto, T., Yoshimatsu, K., Yokomizo, H., et al.[2016]

A study of 27 cancer patients with inflammatory bowel disease (IBD) showed that combining bevacizumab with chemotherapy is safe, with no observed clinical flares of IBD during treatment.

Despite some patients experiencing grade 2 or higher complications like proteinuria and hypertension, the overall safety profile suggests that bevacizumab can be effectively used in patients with either quiescent or moderately active IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. Herrera-Gómez, RG., Grecea, M., Gallois, C., et al.[2022]

In a study of 780 patients with metastatic colorectal cancer in Lombardy, Italy, only 37.8% received bevacizumab according to the approved guidelines, indicating a significant gap between clinical practice and regulatory recommendations.

The treatment was associated with a 1-year survival rate of 74.3% and a median survival time of 20.5 months, with serious adverse events occurring in about 10% of patients, consistent with findings from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in clinical practice: prescribing appropriateness relative to national indications and safety. Bonifazi, M., Rossi, M., Moja, L., et al.[2021]

In a study of 43 patients with metastatic colorectal cancer receiving bevacizumab with FOLFIRI chemotherapy, the treatment was generally well tolerated, with no gastrointestinal perforations reported, but there were notable adverse events including a 9.3% incidence of bleeding and a 14.0% incidence of serious venous thromboembolic events.

The median time to treatment failure was 6.3 months and the median overall survival was 24.4 months, indicating that the efficacy of bevacizumab in this setting aligns with previous clinical trial results, although careful monitoring for serious side effects is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer: an assessment of safety and efficacy in the province of Newfoundland and Labrador. Dranitsaris, G., Edwards, S., Edwards, J., et al.[2021]

Bevacizumab was associated with a higher risk of ocular infections like endophthalmitis and uveitis, while ranibizumab showed increased risks for serious cardiovascular events such as cerebrovascular accidents and myocardial infarctions, based on an analysis of 3180 adverse drug reaction reports.

Pegaptanib did not show significant safety concerns, but was linked to visual impairment and gastrointestinal issues, suggesting it may be a safer option compared to the other two drugs, making bevacizumab a cost-effective choice for treating age-related macular degeneration (AMD) with a similar efficacy to ranibizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions. Biagi, C., Conti, V., Montanaro, N., et al.[2022]

In a clinical trial involving 649 patients with metastatic renal cell carcinoma, the combination of bevacizumab and interferon-alpha2a significantly improved progression-free survival (PFS) compared to placebo, with median PFS times of 10.2 months versus 5.4 months, respectively.

While bevacizumab showed efficacy in delaying disease progression, it did not provide a survival advantage and was associated with a higher incidence of serious adverse events, including bleeding, hypertension, and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab plus interferon for advanced renal cell carcinoma. Summers, J., Cohen, MH., Keegan, P., et al.[2021]

In a phase II study involving 66 patients with previously treated metastatic colorectal cancer, dilpacimab combined with FOLFIRI resulted in a median progression-free survival of only 3.78 months, significantly shorter than the 7.36 months seen with bevacizumab plus FOLFIRI.

Dilpacimab treatment was associated with serious adverse events, including one fatal intestinal perforation, highlighting its poor tolerability compared to bevacizumab, which had no reported serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study. Strickler, JH., Cubillo, A., Liang, JT., et al.[2022]

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]

Bevacizumab (Avastin) significantly improves overall survival when combined with chemotherapy for colorectal cancer, as demonstrated in a case report of a patient with advanced metastases.

In this case, adding bevacizumab to the FOLFOX4 regimen led to a partial response in a patient who had previously relapsed, allowing for a successful salvage hepatic surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of FOLFOX4 and bevacizumab may enable salvage surgery of unresectable liver metastases in colon cancer. Sereno Moyano, M., Casado Sáenz, E., de Castro-Carpeño, J., et al.[2009]

In a retrospective analysis of patients with metastatic colorectal cancer, bevacizumab significantly improved progression-free survival (PFS) and overall survival (OS) in patients aged 65 and older, showing similar benefits to younger patients.

While older patients experienced an increase in thromboembolic events when treated with bevacizumab, no other significant age-related increases in severe adverse events were noted, indicating a manageable safety profile for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. Cassidy, J., Saltz, LB., Giantonio, BJ., et al.[2022]

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

In a phase IV trial involving 209 treatment-naïve patients with metastatic colorectal cancer, the combination of bevacizumab and FOLFIRI resulted in a median progression-free survival (PFS) of 11.1 months and a median overall survival (OS) of 22.2 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse events being mild (grade 1/2), while serious side effects like neutropenia and venous thromboembolic events occurred in over 10% of patients, indicating manageable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Sobrero, A., Ackland, S., Clarke, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06040099

NCT06040099 | A US Study to Evaluate Transarterial ... The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06040099?titles=EMERALD-Y90&rank=1

A US Study to Evaluate Transarterial Radioembolization ... The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D933GC00002

A US study to evaluate transarterial radioembolization ... The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial ...

4. uvahealth.com uvahealth.com/clinical-trials/trial/301080

Clinical Trials | Phase II Single-Arm Study of Durvalumab ... Phase II Single-Arm Study of Durvalumab and Bevacizumab Following Transarterial Radioembolization Using Yttrium-90 Glass Microspheres (TheraSphere™) in ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT06040099

A US Study to Evaluate Transarterial Radioembolization ... The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial ...

6. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_15105.a-us-study-to-evaluate-transarterial-radioembolization-tare-in-combination-with-durvalumab-and-bevacizumab-therapy-in-people-with-unresectable.html

A US Study to Evaluate Transarterial Radioembolization ... The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial ...