A Phase II Study of Atezolizumab and Bevacizumab in Child-Pugh B7 and B8 Hepatocellular Carcinoma (The AB7 Trial)

Howard S Hochster7 sites in 1 country50 target enrollmentMarch 22, 2021

ConditionsUnresectable Hepatocellular Carcinoma

InterventionsAtezolizumab Bevacizumab

DrugsAtezolizumab Bevacizumab

Overview

Phase: Phase 2
Intervention: Atezolizumab
Conditions: Unresectable Hepatocellular Carcinoma
Sponsor: Howard S Hochster
Enrollment: 50
Locations: 7
Primary Endpoint: Frequency and severity of toxicities
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

March 22, 2021

End Date

October 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Howard S Hochster

Responsible Party

Sponsor Investigator

Principal Investigator

Howard S Hochster

Sponsor-Investigator

Big Ten Cancer Research Consortium

Eligibility Criteria

Inclusion Criteria

•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-
•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).

Exclusion Criteria

•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.

Arms & Interventions

Study Treatment

Atezolizumab 1,200 mg IV and bevacizumab 15 mg/kg IV every 3 weeks (on day 1 of each 21-day cycle). Treatment will continue until disease progression or development of unacceptable toxicity.

Intervention: Atezolizumab

Study Treatment

Atezolizumab 1,200 mg IV and bevacizumab 15 mg/kg IV every 3 weeks (on day 1 of each 21-day cycle). Treatment will continue until disease progression or development of unacceptable toxicity.

Intervention: Bevacizumab