Atezolizumab + Bevacizumab Before Surgery for Liver Cancer

Recruiting at 1 trial location

Overseen By Maen Abdelrahim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anti-HBV treatment

Must not be taking: High dose steroids, Immunostimulatory agents

Disqualifiers: Active malignancy, Severe cardiac disease, 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: 7

Duration: 9 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of atezolizumab and bevacizumab before surgery in treating patients with liver cancer that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving the combination of atezolizumab and bevacizumab may help to prevent liver cancer from returning after surgery.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like high-dose steroids, some anticoagulants, and immunosuppressive drugs are restricted. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab plus Bevacizumab for liver cancer?

Research shows that the combination of Atezolizumab and Bevacizumab is effective for treating liver cancer, with a 44% response rate in intermediate-stage cases. It is also considered the gold standard for first-line treatment of unresectable liver cancer, helping some patients achieve complete response when combined with surgery. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab safe for humans?

The combination of Atezolizumab (Tecentriq) and Bevacizumab (Avastin) has been shown to be generally safe in humans, with common side effects including high blood pressure, fatigue, and protein in the urine. Some patients may experience bleeding, so monitoring is recommended, especially for those with liver cancer. ^{1 3 6 7 8}

How is the treatment with atezolizumab and bevacizumab before surgery for liver cancer different from other treatments?

This treatment is unique because it combines atezolizumab and bevacizumab, which are typically used as a first-line treatment for advanced liver cancer, with surgery to potentially reduce the risk of cancer returning after surgery. This approach is novel as there is no established adjuvant (additional) treatment for patients at high risk of liver cancer recurrence after surgery. ^{1 3 9 10 11}

Research Team

Ahmed O. Kaseb

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with resectable liver cancer, who have good liver function (Child-Turcotte-Pugh score A), adequate blood counts, and no severe comorbidities. Participants must not be pregnant or breastfeeding and agree to use two forms of contraception. Exclusions include certain types of liver cancer, recent serious health events like fistulas or bleeding, uncontrolled hypertension, significant pulmonary disease, hypersensitivity to trial drugs, prior treatments for the malignancy within a specific timeframe.

Inclusion Criteria

Serum creatinine ≤ 1.5 × ULN.

I have some limitations in physical activity but can walk and take care of myself.

Women of childbearing potential (WOCBP) and men with partners of child bearing potential agree to prevent pregnancy using two forms of contraception from the date of Informed Consent through 5 months post last dose of study drug.

Exclusion Criteria

You have experienced severe allergic reactions to certain types of medications called chimeric or humanized antibodies.

I have a serious heart condition, such as heart failure or unstable angina.

I have been treated for cancer, have another active cancer, or had cancer in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and bevacizumab intravenously every 21 days for up to 3 cycles

9 weeks

3 visits (in-person)

Surgery

Participants undergo surgery to remove resectable liver cancer

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Therapeutic Conventional Surgery

Trial Overview The study tests atezolizumab plus bevacizumab before surgery in patients with resectable hepatocellular carcinoma. It aims to see if this combination can help the immune system attack the cancer more effectively and prevent it from returning post-surgery by inhibiting tumor growth and spread.

Participant Groups

Group I: Treatment (atezolizumab, bevacizumab) Experimental Treatment 3 Interventions

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery during week 12.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In the phase 3 IMbrave050 study involving 668 patients with high-risk hepatocellular carcinoma, adjuvant treatment with atezolizumab plus bevacizumab significantly improved recurrence-free survival compared to active surveillance, indicating its potential efficacy as a post-surgery treatment.

However, the treatment was associated with a higher incidence of severe adverse events (41% of patients) compared to the active surveillance group (13%), highlighting the need for careful consideration of the benefit-risk profile in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Qin, S., Chen, M., Cheng, AL., et al.[2023]

In a study of 191 patients with unresectable hepatocellular carcinoma (HCC), the combination therapy of atezolizumab and bevacizumab showed similar overall survival and progression-free survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating its efficacy across age groups.

The safety profile of the combination therapy was comparable between older and younger patients, with similar rates of treatment-related adverse events, including severe adverse events, suggesting that older patients can tolerate this treatment as well as younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Vithayathil, M., D'Alessio, A., Fulgenzi, CAM., 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]

In a multicenter study of 121 patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev), the objective response rate was 24% and the disease control rate was 76%, demonstrating real-world efficacy similar to phase III trial results.

The most common severe side effect was an increase in aspartate aminotransferase levels (10.7%), and factors like elevated baseline neutrophil-to-lymphocyte ratio were linked to poorer progression-free and overall survival, indicating the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Cheon, J., Yoo, C., Hong, JY., et al.[2022]

Atezolizumab in combination with bevacizumab has been approved by the FDA for treating unresectable hepatocellular carcinoma (HCC), showing improved overall survival (OS) and progression-free survival (PFS) compared to sorafenib, with a hazard ratio of 0.58 for OS.

The combination therapy resulted in a median PFS of 6.8 months versus 4.3 months for sorafenib, although it was associated with a higher incidence of hemorrhage (25% vs. 17%), highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. Casak, SJ., Donoghue, M., Fashoyin-Aje, L., et al.[2022]

Atezolizumab combined with bevacizumab demonstrated good efficacy in treating advanced hepatocellular carcinoma (HCC), with a pooled overall response rate of 26% and a median overall survival of 14.7 months based on a review of 23 studies involving 3168 patients.

The treatment was well-tolerated, with 83% of patients experiencing any grade adverse events, and 30% experiencing grade 3 or higher adverse events, indicating that while side effects are common, the combination therapy remains a viable first-line option for advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: a single-arm meta-analysis. Gao, X., Zhao, R., Ma, H., et al.[2023]

In a study of 216 patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (AtezoBev), the treatment demonstrated a median overall survival of 14.9 months and a median progression-free survival of 6.8 months, indicating its efficacy in a real-world clinical setting.

Patients with impaired liver function (Child-Pugh class B) experienced similar rates of treatment-related adverse events compared to those with better liver function (Child-Pugh class A), suggesting that AtezoBev is tolerable and may be a viable option for this underserved population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. D'Alessio, A., Fulgenzi, CAM., Nishida, N., et al.[2023]

The combination therapy of atezolizumab and bevacizumab shows potential as a treatment option for patients with both hepatocellular carcinoma and gastric adenocarcinoma.

This finding suggests a possible new approach for managing these concurrent cancers, although further studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocellular carcinoma with gastric adenocarcinoma treated with atezolizumab and bevacizumab. Suga, T., Kimura, Y., Furuya, K., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-Of-Concept Study. [2023]

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

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Conversion Surgery After Atezolizumab Plus Bevacizumab for Primary and Peritoneal Metastasis After Hepatocellular Carcinoma Rupture. [2023]

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

Protocol of the RACB study: a multicenter, single-arm, prospective study to evaluate the efficacy of resection of initially unresectable hepatocellular carcinoma with atezolizumab combined with bevacizumab. [2023]

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

Managing patients treated with bevacizumab combination therapy. [2015]

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

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]

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

FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: a single-arm meta-analysis. [2023]

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

Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. [2023]

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

Hepatocellular carcinoma with gastric adenocarcinoma treated with atezolizumab and bevacizumab. [2023]