protocolSection identificationModule nctId: NCT06339424, orgStudyIdInfo id: 202400156A3, briefTitle: Atezolizumab and Bevacizumab With Photon Radiotherapy for Unresectable Hepatocellular Carcinoma, acronym: PhotonAB, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-03-29, primaryCompletionDateStruct date: 2029-03-30, completionDateStruct date: 2031-03-30, studyFirstPostDateStruct date: 2024-04-01, lastUpdatePostDateStruct date: 2024-04-01, sponsorCollaboratorsModule leadSponsor name: Chang Gung Memorial Hospital, class: OTHER, descriptionModule briefSummary: Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an improved objective response rate (ORR) of 27%, the majority of patients face HCC progression and liver failure \[Finn et al., N Engl J Med 2020\]. Developing a new combined treatment strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient outcomes.Radiation treatment (RT) is highly efficacious in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Importantly, a recent retrospective cohort described that RT combined with atezolizumab plus bevacizumab was associated with favorable median overall survival of 16.1 months (Manzar et al, Cancers 2022). Our preclinical study (Hsieh et al., Science Immunology 2022) revealed that RT combined with PD-L1/PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, thereby potentiating the systemic antitumor T cell responses in murine tumor models. However, whether the combinatorial therapy with RT, atezolizumab, and bevacizumab can trigger synergistic antitumor effects and systemic immune mobilization has not yet been validated in clinical trials for unresectable HCC.Both atezolizumab/bevacizumab and X-ray RT are approved treatment methods for unresectable HCC by the U.S. and Taiwan Food and Drug Administration (FDA). The present phase II non-randomized trial aims to prospectively document the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with conventional photon radiotherapy., conditionsModule conditions: Hepatocellular Carcinoma, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 45, type: ESTIMATED, armsInterventionsModule interventions name: Atezolizumab, interventions name: Bevacizumab, interventions name: Photon radiotherapy, outcomesModule primaryOutcomes measure: Progression free survival (PFS), secondaryOutcomes measure: Local control (LC), secondaryOutcomes measure: Time to progression (TTP), secondaryOutcomes measure: Overall Response Rate (ORR), secondaryOutcomes measure: Overall survival (OS), secondaryOutcomes measure: Incidence and severity of adverse events, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Chang Gung Memorial Hospital at Linkou, city: Taoyuan City, zip: 333, country: Taiwan, geoPoint lat: 24.95233, lon: 121.20193, hasResults: False