SBRT + Atezolizumab/Bevacizumab for Liver Cancer
Recruiting in Palo Alto (17 mi)
Overseen byEdgar Ben-Josef, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Abramson Cancer Center at Penn Medicine
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?A phase I dose escalation and pharmacodynamic study of repeated dose stereotactic body radiotherapy (SBRT) administered with concurrent atezolizumab and bevacizumab for patients with advanced hepatocellular carcinoma (HCC)
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.
What data supports the effectiveness of the treatment Atezolizumab and Bevacizumab for liver cancer?
Research shows that the combination of Atezolizumab and Bevacizumab is effective as a first-line treatment for advanced liver cancer, specifically hepatocellular carcinoma (HCC), and has become the standard of care for this condition.
12345Is the combination of atezolizumab and bevacizumab safe for treating liver cancer?
The combination of atezolizumab and bevacizumab has been shown to be generally safe for treating 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 serious side effects occurred in a small percentage of patients.
16789How is the SBRT + Atezolizumab/Bevacizumab treatment for liver cancer different from other treatments?
This treatment combines SBRT (a precise form of radiation therapy) with the drugs Atezolizumab and Bevacizumab, which is unique because it integrates targeted radiation with immunotherapy and anti-angiogenesis therapy (blocking blood vessel growth to tumors), offering a novel approach for liver cancer that may not be resectable (removable by surgery).
135610Eligibility Criteria
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.
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: study treatment planExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, PA
Loading ...
Who Is Running the Clinical Trial?
Abramson Cancer Center at Penn MedicineLead Sponsor
Abramson Cancer Center of the University of PennsylvaniaLead Sponsor
References
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.
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. [2023]The phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) stage B disease.
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.
Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment. [2022]The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapy for patients with advanced hepatocellular carcinoma (HCC), but the prognosis and treatment pattern after its treatment failure are unclear.
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.
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.
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.
Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience. [2023]Atezolizumab plus bevacizumab is the standard of care for first-line systemic therapy for advanced hepatocellular carcinoma (aHCC). Data on the efficacy and safety of atezolizumab plus bevacizumab in patients with aHCC who have received prior systemic therapy are not available. Methods: Patients with aHCC who received atezolizumab plus bevacizumab after at least one systemic treatment between December 2018 and March 2022 were retrospectively identified in 13 centers in Germany and Austria. Patient characteristics, tumor response rates, progression-free survival (PFS), overall survival (OS), and adverse events (AE) were analyzed. Results: A total of 50 patients were identified; 41 (82%) were male. The median age at initiation of treatment with atezolizumab plus bevacizumab was 65 years, 41 (82%) patients had cirrhosis, 30 (73%) Child A, 9 (22%) B, and 2 (5%) C. A total of 34 patients (68%) received atezolizumab plus bevacizumab in the second-line setting and 16 (32%) in later lines. The best radiologic tumor responses were complete remission (2%), partial remission (30%), stable disease (36%), and progressive disease (18%), resulting in an objective response rate of 32% and a disease control rate of 68%. Median OS was 16.0 months (95% confidence interval 5.6-26.4 months), and median PFS was 7.1 months (95% confidence interval 4.4-9.8 months). AE grades 3-4 were observed in seven (14%) and resulted in death in three patients (6%). There were five (10%) bleeding events with a grade ≥ 3, including one (2%) with a fatal outcome. Conclusions: Atezolizumab plus bevacizumab is effective in patients with aHCC who did not have access to this option as first-line therapy. The safety profile was consistent with previous reports.
Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. [2021]Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC.
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.