SBRT + Atezolizumab + Bevacizumab in Resectable HCC

NCT04857684 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 20-570
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hepatocellular Carcinoma; Resectable Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Resectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

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

  Assessed by CTCAE v5.0

  From enrollment to end of treatment, up to 6 months

Secondary Outcomes (6)

• Objective response rate (ORR)

  From enrollment to end of treatment, up to 3 months

• Proportion of patients who proceed to surgery after neoadjuvant treatment.

  From enrollment to end of treatment, up to 3 months

• Proportion of patients who undergo a microscopic margin-negative (R0) resection

  From enrollment to end of treatment, up to 3 months

• Complete response (CR)

  From enrollment to end of treatment, up to 3 months

• Overall survival (OS)

  From enrollment to end of treatment, up to 2 years

Study Arms (1)

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Bevacizumab; Radiation: Stereotactic Beam Radiation Therapy (SBRT)

Interventions

Atezolizumab DRUG

Intravenous Infusion

Also known as: Tecentriq

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

Bevacizumab DRUG

Intravenous Infusion

Also known as: Avastin

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

Stereotactic Beam Radiation Therapy (SBRT) RADIATION

External beam radiation

Also known as: Radiation Therapy

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• Jennifer Y Wo, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 23, 2021
• Study Start: June 18, 2021
• Primary Completion: April 29, 2026
• Study Completion (Estimated): April 29, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)