SBRT + Atezolizumab/Bevacizumab for Liver Cancer

Overseen By Taylor Siegal

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center at Penn Medicine

Disqualifiers: Curative surgery, Curative ablation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on dose escalation

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and effects of combining two drugs, atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenic drug), with a precise form of radiation therapy called stereotactic body radiotherapy (SBRT) for treating liver cancer. It targets patients with advanced liver cancer (hepatocellular carcinoma) that cannot be treated with surgery or ablation. Eligible participants require systemic therapy due to the extent of their disease or other health issues. The study examines how this combination affects the cancer and monitors for any side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination therapy.

Will I have to stop taking my current medications?

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

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

Research has shown that the combination of atezolizumab and bevacizumab is generally well-tolerated in patients with advanced liver cancer. One study found that this combination helped patients live longer and slowed disease progression. No unexpected side effects emerged, indicating a predictable safety profile.

Regarding SBRT (stereotactic body radiation therapy), studies indicate it effectively controls liver cancer locally with few severe side effects. Patients often experience fewer complications compared to surgery. Overall, SBRT's side effects are manageable and less severe.

Together, these treatments have proven effective and generally safe for liver cancer, based on previous studies. However, the current trial will further assess safety as it involves combining these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Atezolizumab, Bevacizumab, and SBRT for liver cancer because it offers a multi-pronged approach to treatment. Atezolizumab is an immunotherapy drug that helps the immune system recognize and destroy cancer cells, while Bevacizumab is an antibody that targets and inhibits blood vessel growth in tumors, potentially starving them of nutrients. Combining these with SBRT, a precise form of radiation therapy, may enhance the overall effectiveness by directly targeting cancer cells with minimal damage to surrounding tissue. This innovative approach could potentially improve outcomes compared to standard treatments, which often rely on surgery, chemotherapy, or less targeted radiation therapies.

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

Research shows that using atezolizumab and bevacizumab together effectively treats advanced liver cancer, specifically hepatocellular carcinoma (HCC). Studies have found that this combination not only extends patient survival but also slows disease progression. For example, the IMbrave150 trial found a 42% lower risk of death compared to traditional treatments like sorafenib. Additionally, research indicates that stereotactic body radiation therapy (SBRT) effectively controls liver cancer and extends patient survival. SBRT has a 95% success rate in controlling cancer for five years and outperforms treatments like radiofrequency ablation (RFA). This trial will evaluate the combination of SBRT with atezolizumab and bevacizumab, offering promising hope for managing advanced liver cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Edgar Ben-Josef, MD

Principal Investigator

Abramson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced liver cancer (HCC) who can't have surgery or ablation due to the extent of disease, other health issues, or technical reasons and need systemic therapy.

Inclusion Criteria

My liver cancer cannot be treated with surgery or ablation, and I need drug treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeated dose stereotactic body radiotherapy (SBRT) with concurrent atezolizumab and bevacizumab

Varies based on dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab and Bevacizumab
• SBRT

Trial Overview

The study tests how safe and effective it is to give repeated doses of SBRT (a type of focused radiation therapy) along with two drugs, atezolizumab and bevacizumab, in treating liver cancer.

How Is the Trial Designed?

Group I: study treatment plan Experimental Treatment 1 Intervention

Patients will be enrolled in a Rolling 6 clinical trial design1. This study design retains sensitivity to identifying DLTs while having the benefit of decreasing accrual time given the long DLT period required to assess radiation toxicity. In this trial design, up to 6 patients can be enrolled at a time onto a dose level while awaiting DLT assessment. Established rules guide the decision for enrolling onto the current, next highest, or previous dose level based on the number of participants currently enrolled in a given cohort, the number of radiation-attributable dose-limiting toxicities (ra-DLTs) observed, and the number of patients with immature toxicity data. If the MTD is not reached after 6 patients have enrolled on dose level 3 (three 17Gy fractions of SBRT) and have completed toxicity evaluations, then the recommended phase 2 dose will be determined based on an analysis of the efficacy of the combination

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

Approved in United States as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in Canada as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in Japan as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Published Research Related to This Trial

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 41 patients with advanced hepatocellular carcinoma who failed first-line treatment with atezolizumab and bevacizumab, the median post-first-line survival was 5.9 months, significantly influenced by liver function status after treatment failure.

Patients with better liver function (Child-Pugh A) had a median survival of 9.6 months compared to only 3.8 months for those with Child-Pugh B and 1.2 months for Child-Pugh C, highlighting the importance of liver reserve and the benefit of receiving second-line therapy, which improved survival to a median of 8.0 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment. Chen, CT., Feng, YH., Yen, CJ., et al.[2022]

Atezolizumab plus bevacizumab therapy shows promising efficacy for advanced hepatocellular carcinoma (HCC), achieving an objective response rate of 15.6% and a high disease control rate of 93.8% among 34 patients, regardless of liver function or treatment line.

Following the failure of atezolizumab plus bevacizumab therapy, lenvatinib treatment can also be effective, but careful monitoring of liver function is necessary, as indicated by significant reductions in liver function scores in patients receiving lenvatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. Komatsu, S., Yano, Y., Fujishima, Y., et al.[2022]

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]

In a phase III study involving 501 patients with unresectable hepatocellular carcinoma (HCC), those with baseline BCLC stage B disease showed a trend towards improved overall survival (OS) and progression-free survival (PFS) when treated with atezolizumab plus bevacizumab compared to sorafenib, with hazard ratios of 0.63 and 0.64, respectively.

The objective response rates (ORR) were significantly higher for the atezolizumab plus bevacizumab group (43% and 50% using different assessment criteria) compared to the sorafenib group (26% and 30%), indicating that this combination therapy may provide more effective tumor response in patients with BCLC stage B HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study. Kudo, M., Finn, RS., Galle, PR., et al.[2023]

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]

In a real-world study of 61 patients with hepatocellular carcinoma (HCC), the combination of atezolizumab and bevacizumab showed a median progression-free survival (PFS) of 5.4 months and an objective response rate (ORR) of 35.3%.

The treatment was found to be safe, with a high incidence of adverse events (98.0%), primarily hepatic disorders, but it remained effective even in patients with prior treatment histories or varying liver function as indicated by albumin-bilirubin (ALBI) grades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. Iwamoto, H., Shimose, S., Noda, Y., et al.[2021]

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]

In a multicenter study involving 30 patients with unresectable hepatocellular carcinoma and extrahepatic portal vein tumor thrombus, the combination of intensity-modulated radiotherapy (IMRT) with systemic atezolizumab and bevacizumab (atezo/bev) resulted in a high objective response rate of 76.6% and a median overall survival of 9.8 months.

The treatment was found to have an acceptable safety profile, with neutropenia being the most common adverse event, and no treatment-related deaths reported, suggesting that this combination therapy could be a promising option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study. Wang, K., Xiang, YJ., Yu, HM., et al.[2023]

Atezolizumab plus bevacizumab shows efficacy in patients with advanced hepatocellular carcinoma (aHCC) who have previously received systemic therapy, achieving an objective response rate of 32% and a median overall survival of 16 months based on a study of 50 patients.

The safety profile of this treatment was consistent with earlier studies, with 14% of patients experiencing severe adverse events, including three deaths, indicating that while effective, careful monitoring for serious side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience. Sinner, F., Pinter, M., Scheiner, B., et al.[2023]

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