Atezolizumab+Bevacizumab+SBRT in Unresectable HCC

NCT05096715 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-286
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is evaluating the safety and tolerability of the drugs atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) for treating unresectable hepatocellular carcinoma. This study involves the following interventions:

• Atezolizumab
• Bevacizumab
• Stereotactic body radiation therapy (SBRT)

Conditions

Unresectable Hepatocellular Carcinoma

Keywords

Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity Rate

  Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  18 weeks

Secondary Outcomes (5)

• Progression free survival (PFS)

  5 years

• Overall Survival (OS)

  5 years

• In-field response rate

  5 years

• Change in Child-Pugh Score

  2.5 years

• Out of field response rate

  2.5 years

Study Arms (1)

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

EXPERIMENTAL

Study will begin with a safety lead of 6 participants to determine the maximum tolerated dose (MTD) of Stereotactic beam radiation therapy (SBRT) with atezolizumab and bevacizumab followed by study expansion to 14 more participants after maximum tolerated dose (MTD) is established. Safety Lead-In: 6 cycles/18 weeks (study cycle is 3 weeks/21 days) * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-6: Atezolizumab + Bevacizumab (1x) every 3 weeks Expanded Study: * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-End:Atezolizumab + Bevacizumab (1x) every cycle

Drug: Atezolizumab; Drug: Bevacizumab; Radiation: Stereotactic body 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: Mvasi, Zirabrev

Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab

Stereotactic body 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 diagnosis of hepatocellular carcinoma (HCC) that is deemed unsuitable for surgical resection, transplant, or radiofrequency ablation (RFA). Participants may have up to 5 lesions with a total maximal tumor dimension of \< 20 cm, and no one lesion \> 15 cm. Diagnosis may be confirmed by at least 1 criteria listed below:
• Histologically or cytologically proven diagnosis of HCC within 180 days prior to study registration.
• At least 1 solid liver lesion or vascular tumor thrombus (involving portal vein, IVC, and/or hepatic vein) \> 1 cm with arterial enhancement and delayed washout on multiphasic CT or MRI. Radiologic imaging evaluation must occur within 28 days prior to study registration.
• Enhancing vascular thrombosis demonstrating arterial enhancement and delayed washout of multiphasic MRI. Radiologic imaging evaluation must occur within 30 days prior to study registration.
• 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.
• Small volume extrahepatic disease permitted, defined as \<2.0 cm in sum of maximal diameters (e.g. presence of one 1.8 cm metastatic lymph node, or two 0.8 cm lung lesions are allowed). Bony lesions are included in the \<2.0 cm of extrahepatic disease. Note that benign periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is \> 2.0 cm. Radiologic imaging of chest, abdomen, and pelvis via CT or MRI is required within 28 days prior to study registration. CT with contrast is required unless contrast is contraindicated.
• Participants may have received transarterial chemoembolization (TACE) or drug eluting beads (DEB). A 2 week (14 day) washout period is required prior to initiating study treatment.
• Age ≥18 years at the time of signing informed consent document.
• ECOG performance status 0-1.
• Child-Pugh A liver function within 7 days of study registration.
• Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C) within 7 days of study registration.
• No evidence of significant portal hypertension.
• Participants must have adequate organ and marrow function as defined the following laboratory results, obtained within 7 days prior to study registration:
• absolute neutrophil count ≥1,500/mcL
• absolute lymphocyte count ≥500/mcL

You may not qualify if:

• Prior systemic therapy
• Prior radiation to the region of the liver that would result in excessive doses to normal tissues due to overlap of RT fields is not allowed. Radiotherapy within 28 days and abdominal/pelvic radiotherapy within 60 days prior to initiation of study treatment are not allowed. Exception for palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment.
• Prior selective internal radiotherapy (SIRT) or hepatic arterial Yttrium therapy, at any time.
• Direct tumor extension into the stomach, duodenum, small bowel, or large bowel.
• Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 2 cm, in sum of maximal diameters (e.g. presence of one 2.4 cm metastatic lymph node or two 1.2 cm lung lesions).
• Known fibrolamellar HCC, sarcomatoid HCC, or biphenotypic HCC.
• History of leptomingeal disease.
• GI bleed within 6 months prior to study registration.
• Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (\<30 mm from the carina) of large volume. Participants with vascular invasion of the portal or hepatic veins may be enrolled.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids

Sponsors & Collaborators

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

Study Sites (3)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Interventions

atezolizumab; Bevacizumab; Radiosurgery; Radiotherapy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jennifer Y Wo, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Y Wo, MD

CONTACT

(617) 726-6050; jwo@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: 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: August 30, 2021
• First Posted: October 27, 2021
• Study Start: August 23, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2032
• Last Updated: February 18, 2026

Record last verified: 2026-02

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 (3)