A Study of Atezolizumab and Bevacizumab in Hepatocellular Carcinoma

Completed · Phase 2

Conditions studied: Unresectable Hepatocellular Carcinoma

In brief

This will be a nonrandomized, single arm feasibility study with the primary goal of evaluating the safety profile of the combination of atezolizumab and bevacizumab in patients with advanced/metastatic HCC with Child-Pugh B7 and B8 liver disease who have received no prior systemic therapy.

Key facts

Study ID

NCT04829383

Run by

Howard S Hochster

People needed

6

Starts

2021-03-22

Expected to finish

2024-10-15

Last updated by the study team

2026-06-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subject must meet all of the following applicable inclusion criteria to participate in this study:
• Written informed consent and HIPAA authorization for release of personal health information must be obtained either from the subject or their representative. See protocol. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1.
• Locally advanced, metastatic, or unresectable hepatocellular carcinoma that has not received prior systemic therapy. Note: if no prior histologic diagnosis exists, prefer fresh biopsy if it is both safe and feasible. If fresh biopsy is not safe and feasible, imaging criteria may be used for diagnosis as per AASLD criteria in cirrhotic patients (please see www.aasld.org for up to date guidelines).
• Child Pugh Class B7 or B8 liver dysfunction or cirrhosis with the following limitations:
• Bilirubin ≤ 3 mg/dL
• Albumin ≥ 2.8 g/dL
• INR ≤ 1.7
• Absent to slight [CP=1 to 2] (no moderate [CP=3]) ascites (Also see exclusion criteria).
• No clinically significant encephalopathy (Also see exclusion criteria).
• At least 1 untreated measurable lesion according to RECIST 1.1.
• Willingness to undergo fresh tumor biopsy at baseline if safe and feasible. Note: archival tissue may be used at baseline provided histologic diagnosis was made and sufficient tissue is available for NGS analysis.
• NGS analysis must be requested from archival tissue or fresh biopsy (if applicable) as per standard of care. Foundation One CDX is the preferred platform. Prior NGS sequencing results (including from another platform) will be accepted if NGS sequencing was previously obtained (please see protocol).
• Demonstrate adequate bone marrow and organ function as defined below:
• Hematologic
• Absolute neutrophil count (ANC) ≥ 1,000/mcL
• Lymphocyte count ≥ 0.5 x 10\^9/L (500uL)
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Platelet count ≥ 70,000/mcL
• Renal
• Serum creatinine OR calculated* serum creatinine clearance (GFR can be used in place of creatinine or creatinine clearance) ≤ 1.5 x ULN OR ≥ 30 mL/min for participants with creatinine levels > 1.5 x institutional ULN *calculate serum creatinine clearance using the standard Coccroft-Gault formula
• Urine protein: Urine dipstick for proteinuria < 2+ within 7 days prior to start of study treatment *Patients with with ≥ 2+ proteinuria on dipstick analysis at baseline should undergo a 24-hour urine collection which must demonstrate < 1g of protein in 24 hours.
• Hepatic
• AST (SGOT) and ALT (SGPT) ≤ 8 x ULN

You may not qualify if…

• Subjects meeting any of the criteria below may not participate in the study:
• Histologic diagnosis of fibrolamellar or sarcomatoid HCC or mixed cholangiocarcinoma-HCC.
• Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 21 days of first planned dose of study therapy (within 14 days for palliative radiation). Patients who have had major surgery within 4 weeks of start of study therapy or anticipation of need for a major surgical procedure during the study.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > CTCAE Grade 1) with the exception of alopecia or neuropathy.
• Patients who have received prior systemic therapy for HCC.
• Patients who have received prior immunotherapy.
• Patients with clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control within 3 months prior to the first dose of study treatment. Note: Patients with ascites meeting eligibility criteria who require pharmacologic intervention (e.g. diuretics) to maintain symptomatic control and who have been on stable doses of diuretics for 2 months prior to the first dose of study treatment are eligible.
• Patients with clinically meaningful encephalopathy, defined as a history of hepatic encephalopathy within 6 months prior to first dose of study treatment or requirement for medications to prevent or control encephalopathy (e.g. lactulose, rifaximin).
• Any of the following additional high-risk features:
• Patients with untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. Note: 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 with appropriate management of varices (if applicable) within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
• History of esophageal and/or gastric hemorrhage within 3 months prior to study treatment.
• History of hemoptysis (< 2.5 mL of bright red blood per episode) within 1 month prior to study treatment.
• History of intracranial hemorrhage within 1 month prior to study treatment.
• History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment. Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure.
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture within 30 days prior to start of study treatment.
• Metastatic disease that involves major airways or blood vessels. Patients with vascular invasion of the portal or hepatic veins may be enrolled.
• Significant vascular disease (e.g. aortic aneurysm requiring surgical repair) or vasculitis within 6 months prior to initiation of study treatment.
• History of arterial thrombotic event (e.g. myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack) within 6 months prior to initiation of study treatment.
• Chronic or recent (within 10 days of first dose of study treatment) use of aspirin > 325 mg/day, dipyramidaole, ticlopidine, clopidogrel, or dilostazol. Note: Use of aspirin < 325 mg/day is allowed.
• History of venous thromboembolic event (e.g. deep vein thrombosis, pulmonary embolism, portal vein thrombosis, or any other significant thromboembolism) must be on a stable dose of anticoagulation for 1 month prior to initiation of study treatment and must have completely treated varices.
• Use of Coumadin-like products or full dose oral or parenteral anticoagulants. Use of prophylactic low dose anticoagulation, unfractionated heparin or LMWH is allowed.
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• Core biopsy or other minor surgical procedure within 3 days prior to the first dose of bevacizumab.
• History of intestinal obstruction. Note: Patients with previous intestinal obstruction may be enrolled if they have received definitive treatment for symptom resolution.
• History of inflammatory process within 6 months prior to start of study treatment including but not limited to active peptic ulcer disease, diverticulitis or colitis.

Where it is running

• University of Illinois Cancer Center — Chicago, Illinois, United States
• Indiana University Melvin and Bren Simon Comprehensive Cancer Center — Indianapolis, Indiana, United States
• University of Nebraska Medical Center — Omaha, Nebraska, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• New York University Clinical Cancer Center — New York, New York, United States
• DHR Health Institute for Research and Development — Edinburg, Texas, United States
• Univeristy of Wisconsin — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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