Atezolizumab + Bevacizumab + SBRT for Liver Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Jennifer Y Wo, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Massachusetts General Hospital

Must be taking: Anti-HBV therapy

Must not be taking: Anticoagulants, NSAIDs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This research study is evaluating the safety and tolerability of the drugs atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) for treating unresectable hepatocellular carcinoma. This study involves the following interventions: * Atezolizumab * Bevacizumab * Stereotactic body radiation therapy (SBRT)

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, there are certain restrictions on medications like full-dose anticoagulants and NSAIDs, and a washout period is required for some prior treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Atezolizumab + Bevacizumab + SBRT for liver cancer?

Research shows that the combination of atezolizumab and bevacizumab is effective in increasing overall survival for patients with advanced liver cancer, and it has become a standard treatment option. This combination has been proven to be superior to other treatments like sorafenib for liver cancer that cannot be treated with surgery or other local methods. ^{1 2 3 4 5}

Is the combination of atezolizumab, bevacizumab, and SBRT safe for liver cancer treatment?

The combination of atezolizumab and bevacizumab has been shown to be generally safe for patients with advanced liver cancer, with common side effects including high blood pressure, fatigue, and protein in the urine. However, there is a higher risk of bleeding, and patients should be evaluated for varices (enlarged veins) before starting treatment. The safety of adding SBRT to this combination has not been specifically addressed in the available studies. ^{3 5 6 7 8}

How is the treatment of Atezolizumab, Bevacizumab, and SBRT for liver cancer different from other treatments?

This treatment combines two drugs, atezolizumab and bevacizumab, with stereotactic body radiation therapy (SBRT), offering a novel approach that may improve survival in liver cancer patients compared to traditional treatments like sorafenib. Atezolizumab helps the immune system attack cancer cells, bevacizumab blocks blood supply to tumors, and SBRT delivers precise radiation, potentially enhancing the overall effectiveness. ^{1 2 3 5 9}

Eligibility Criteria

This trial is for adults with unresectable hepatocellular carcinoma (liver cancer), who have not had certain prior treatments, and whose liver function is relatively preserved (Child-Pugh A). They should have no more than 5 liver lesions, no severe portal hypertension or significant heart disease, and must not be pregnant or breastfeeding. Contraception use is required for participants of childbearing potential.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I have had TACE or DEB treatments with a 2-week break before this trial.

My liver is functioning well according to a recent test.

Exclusion Criteria

History of severe anaphylactic reactions to specific substances

My high blood pressure is not well controlled.

I do not have any unmanaged ongoing illnesses.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Safety lead-in phase to determine the maximum tolerated dose (MTD) of SBRT with atezolizumab and bevacizumab

18 weeks

6 cycles (1 visit per cycle)

Expanded Study

Participants receive Atezolizumab and Bevacizumab with SBRT, followed by Atezolizumab and Bevacizumab every cycle

Variable, based on safety and benefit

1 visit per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Bevacizumab (Monoclonal Antibodies)
• Stereotactic body radiation therapy (SBRT) (Radiation)

Trial Overview The study tests the combination of atezolizumab and bevacizumab drugs with stereotactic body radiation therapy (SBRT) to see if it's safe and tolerable for treating liver cancer that can't be removed by surgery. Participants will receive these medications alongside targeted radiation treatment.

Participant Groups

Group I: Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab Experimental Treatment 3 Interventions

Study will begin with a safety lead of 6 participants to determine the maximum tolerated dose (MTD) of Stereotactic beam radiation therapy (SBRT) with atezolizumab and bevacizumab followed by study expansion to 14 more participants after maximum tolerated dose (MTD) is established. Safety Lead-In: 6 cycles/18 weeks (study cycle is 3 weeks/21 days) * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-6: Atezolizumab + Bevacizumab (1x) every 3 weeks Expanded Study: * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-End:Atezolizumab + Bevacizumab (1x) every cycle

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Beth Israel Deaconess Medical Center Boston, MA

Dana-Farber Cancer Institute Boston, MA

Massachusetts General Hospital Cancer Center Boston, MA

Who Is Running the Clinical Trial?

Massachusetts General Hospital Lead Sponsor

Genentech, Inc. Industry Sponsor

References

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

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. [2022] The combination of atezolizumab and bevacizumab increases overall survival compared with sorafenib in advanced hepatocellular carcinoma (HCC). Its approval by the FDA has launched a new era of combination therapies in advanced and earlier settings that are likely to reshape the management of HCC across all disease stages.See related article by Casak et al., p. 1836.

2. 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] Atezolizumab plus bevacizumab was approved in 2020 as a first-line treatment for advanced hepatocellular carcinoma (HCC). The purpose of this study was to assess the curative effect and tolerability of the combination treatment in advanced HCC.

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

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022] Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings.

4. Netherlands pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. [2022] The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, becoming the standard of care of systemic therapy.

5. Switzerland 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. [2023] The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients.

6. 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] On May 29, 2020, the FDA approved atezolizumab for use in combination with bevacizumab, for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC) with no prior systemic treatment. The approval was based on data from Study IMbrave150, which randomly allocated (2:1) patients to receive either atezolizumab plus bevacizumab (atezolizumab-bevacizumab) or sorafenib. Overall survival (OS) and independently assessed progression-free survival (PFS) in the intent-to-treat population were the primary endpoints. At the time of the primary analysis, the estimated median OS could not be estimated in the atezolizumab-bevacizumab arm and was 13.2 months in the sorafenib arm [HR, 0.58; 95% confidence interval (CI), 0.42-0.79]. The estimated median PFS was 6.8 months (95% CI, 5.8-8.3) and 4.3 months (95% CI, 4.0-5.6) in the atezolizumab-bevacizumab and sorafenib arms, respectively. Adverse reactions occurring in >20% of patients receiving atezolizumab-bevacizumab were hypertension, fatigue/asthenia, and proteinuria. Adverse reactions occurring in >20% of patients receiving sorafenib were palmar-plantar erythrodysesthesia, diarrhea, hypertension, and decreased appetite. Hemorrhage was reported more frequently in patients receiving atezolizumab-bevacizumab (25%) than in patients receiving sorafenib (17%). An evaluation for the presence of varices is recommended within 6 months of initiation of atezolizumab-bevacizumab in patients with HCC. Approval of atezolizumab-bevacizumab is likely to change the treatment paradigm for HCC, given that treatment with atezolizumab-bevacizumab resulted in improved OS and PFS compared with sorafenib, an accepted standard of care for first-line treatment of patients with unresectable HCC.See related commentary by Castet et al., p. 1827.

7. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023] Atezolizumab-bevacizumab (atezo-bev) is recommended as first-line therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, its effectiveness and safety in other populations, including those with Child-Turcotte-Pugh (CTP) class B cirrhosis, is unclear.

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab in patients with child-Pugh B advanced hepatocellular carcinoma. [2023] Atezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III IMbrave150 trial. However, patients with Child-Pugh B HCC were excluded in the abovementioned prospective trial. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in patients with Child-Pugh B HCC.

9. Switzerland pubmed.ncbi.nlm.nih.gov

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab. [2023] In the Phase 3 IMbrave150 trial (NCT03434379), atezolizumab + bevacizumab demonstrated a clinically meaningful survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (HCC), including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. We used IMbrave150 data to investigate the safety and risk of viral reactivation or flare in infected patients treated with atezolizumab + bevacizumab or sorafenib.