SBRT + Atezolizumab + Bevacizumab in Resectable HCC

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria: - Participants must have a diagnosis of hepatocellular carcinoma that is localized to the liver, has no radiographic evidence of macrovascular invasion, and is deemed surgically resectable. The diagnosis may be obtained radiographically (i.e. having a LiRADS or OPTN category 5 liver lesion) or by histologic diagnosis from a core biopsy or cytology specimen. Radiographic evaluation should occur within approximately 30 days prior to enrollment. - Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as =20 mm (=2 cm) by chest x-ray or as =10 mm (=1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease. - Participants must have Child-Pugh A liver function (see Appendix A). - No prior therapy directed against the index hepatocellular carcinoma lesion is allowed - Age =18 years at the time of signing the informed consent document. - ECOG performance status = 1 (Karnofsky =60%, see Appendix B). - Participants must have adequate organ and marrow function as defined below: - leukocytes =3,000/mcL - absolute neutrophil count =1,500/mcL - platelets =100,000/mcL - total bilirubin = 2 × institutional upper limit of normal (ULN) - AST(SGOT)/ALT(SGPT) = 3 × institutional ULN - creatinine = 1.5 × institutional ULN OR - estimated glomerular filtration rate (GFR) =50 mL/min/1.73 m2 (according to the Cockcroft-Gault formula) - Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. - Documented virology status of hepatitis, as confirmed by screening tests for HBV and HCV - For patients with active HBV: HBV DNA <500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir) - Patients with HCV, either with resolved infection (as evidenced by detectable antibody and negative viral load) or chronic infection (as evidenced by detectable HCV RNA), are eligible. - Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. - Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better. - The effects of the combination of radiation and atezolizumab plus bevacizumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to either abstain from sexual intercourse or use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of atezolizumab and bevacizumab administration. - Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: - Known fibrolamellar HCC, sarcomatoid HCC, or mixed/biphenotypic cholangiocarcinoma-HCC. - Radiographic evidence of metastasis to lymph nodes or other extra-hepatic sites. - History of hepatic encephalopathy, moderate or severe ascites. - Coinfection with HBV and HCV. Patients with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV. - Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure. - A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment - Inadequately controlled hypertension, defined as systolic blood pressure (BP) <150 mmHg and/or diastolic BP < 100 mmHg (average of at least three readings at two or more sessions). Anti-hypertensive therapy to achieve these parameters is allowed. - History of hypertensive crisis or hypertensive encephalopathy. - Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment - History of hemoptysis (> 2.5 mL of bright red blood per episode) within 1 month prior to initiation of study treatment - Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) - Current or recent (< 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. Prophylactic anticoagulation for the patency of venous access devices allowed, provided the activity of the agent results in an INR < 1.5 x ULN and aPPT is within normal limits within 14 days prior to initiation of study treatment. For prophylactic use of anticoagulants or thrombolytic therapies, the approved dose as described on the local label may be used. - Current or recent (< 10 days prior to initiation of study treatment) use of aspirin (> 325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol. - Participants who are receiving any other investigational agents. - Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to initiation of study systemic therapy. - History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment. - History of intestinal obstruction and/orclinical signs or symptoms of GI obstruction, including subocclusive or occlusive syndrome related to the underlying disease, or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to initiation of study systemic therapy. Patients with signs or symptoms of subocclusive o

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of patients with grade 3-4 treatment-related adverse events as assessed by CTCAE v5.0

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR);Proportion of patients who proceed to surgery after neoadjuvant treatment.;Proportion of patients who undergo a microscopic margin-negative (R0) resection;Complete response (CR);Overall survival (OS);Recurrence-free survival (RFS) after resection

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