SBRT + Atezolizumab + Bevacizumab for Liver Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Joseph W Franses, MD, PHD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: Anticoagulants, NSAIDs, Immunosuppressants, others

Disqualifiers: Metastasis, Hypertension, Autoimmune disease, others

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study is evaluating the safety and tolerability of neoadjuvant stereotactic body radiation therapy (SBRT) with atezolizumab and bevacizumab for treating resectable hepatocellular carcinoma. This study involves the following study interventions: * Atezolizumab * Bevacizumab * Stereotactic Beam Radiation Therapy (SBRT) * Surgery

Do I need to stop my current medications to join the trial?

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

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

Research shows that the combination of atezolizumab and bevacizumab is effective and safe for treating advanced liver cancer, improving overall survival compared to previous treatments. This combination is now a standard treatment option for advanced liver cancer.

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Is the combination of SBRT, Atezolizumab, and Bevacizumab 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 checked for varices (enlarged veins) before starting treatment.

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

This treatment combines SBRT (a precise form of radiation therapy) with Atezolizumab and Bevacizumab, which are drugs that help the immune system fight cancer and block blood supply to tumors, respectively. This combination is unique because it integrates targeted radiation with immunotherapy and anti-angiogenic therapy, offering a novel approach for treating advanced liver cancer.

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Eligibility Criteria

This trial is for adults with resectable hepatocellular carcinoma (a type of liver cancer) who have good liver function (Child-Pugh A), no history of certain bleeding events or severe allergies, and are not pregnant. They must be able to understand the study and consent to it, have measurable disease without vascular invasion, and agree to use contraception.

Inclusion Criteria

The number of certain white blood cells in your body, called neutrophils, must be at least 1,500 per microliter.

I am 18 years old or older.

I have not received any treatment for my liver cancer lesion.

Exclusion Criteria

Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies

Evidence of bleeding diathesis or significant coagulopathy

I have had lung conditions like pulmonary fibrosis or pneumonitis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic beam radiation therapy (SBRT) on three treatment days arranged on an every-other-day basis

1 week

3 visits (in-person)

Treatment

Participants receive two 3-week cycles of atezolizumab and bevacizumab

6 weeks

Atezolizumab on day 1 of each cycle, Bevacizumab 1x weekly

Surgery

Surgery is performed 6-8 weeks after the last infusions of atezolizumab and bevacizumab

6-8 weeks post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Participant Groups

The trial tests the combination of SBRT (a precise form of radiation therapy), Atezolizumab, Bevacizumab, followed by surgery in patients with resectable liver cancer. It aims to assess how safe this treatment sequence is and how well patients tolerate it.

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

Participants will: * undergo a pre-treatment biopsy with fiducial marker placement * receive Stereotactic beam radiation therapy (SBRT) on three treatment days which will be arranged on an every-other-day basis * receive two 3-week (21 days) cycles of atezolizumab plus bevacizumab * receive Atezolizumab on day 1 for 2 study cycles. * receive Bevacizumab 1x weekly for 2 study cycles * Surgery after SBRT and the two cycles of atezolizumab and bevacizumab, unless participants are otherwise informed by their doctor. The planned surgery will take place 6-8 weeks after the last infusions of atezolizumab and bevacizumab.

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:

Massachusetts General Hospital Cancer Center Boston, MA

Who Is Running the Clinical Trial?

Massachusetts General Hospital Lead Sponsor

Genentech, Inc. Industry Sponsor

References

1. 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.

2. 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.

3. 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.

4. 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.

5. Greece pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. [2022] Atezolizumab plus bevacizumab therapy is the new standard treatment option for advanced hepatocellular carcinoma (HCC). The clinical details and sequential course after atezolizumab plus bevacizumab therapy remain to be determined.

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 &gt;20% of patients receiving atezolizumab-bevacizumab were hypertension, fatigue/asthenia, and proteinuria. Adverse reactions occurring in &gt;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. United States pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. [2023] Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC.

8. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023] Atezolizumab plus bevacizumab and lenvatinib are the current first-line systematic therapy for unresectable hepatocellular carcinoma (uHCC). However, the selection of initial treatment among the two therapies are controversial. This meta-analysis aims to compare efficacy and safety between atezolizumab plus bevacizumab and lenvatinib.

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab. [2023] Radiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients.