Study of Atezolizumab and Bevacizumab With Y-90 TARE in Patients With Unresectable Hepatocellular Carcinoma (HCC)

NCT04541173 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GI19-405
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, multi-center, randomized phase II study comparing the Y90 TARE followed by bevacizumab and atezolizumab treatment to the Y90 TARE treatment alone in unresectable advanced stage HCC.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) by RECIST 1.1

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.

  Up to a maximum of 16 months.

Secondary Outcomes (8)

• Adverse Events

  14 months

• Progression Free Survival by mRECIST

  Up to a maximum of 16 months.

• Time to Progression (TTP) by mRECIST

  Up to a maximum of 16 months.

• Overall Response Rate (ORR) by mRECIST

  Up to a maximum of 16 months

• Overall Survival (OS)

  Upto a maximum of 18 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

TARE alone

Other: Y-90 TARE

Arm B

EXPERIMENTAL

TARE then Bevacizumab and Atezolizumab

Other: Y-90 TARE; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Y-90 TARE OTHER

This plan will involve treating the predominant liver lesions with segment Y-90 TARE using predetermined dosimetry, while keeping FLR equal or greater than 40% (FLR is estimated by excluding the liver volume of Y-90 infused distribution). The maximal amount of Y-90 TARE treatment will be limited to only one lobe of the liver if segmental Y-90 TARE is not possible to treat the predominant lesion. Since segmental Y-90 TARE may result in less long term liver damage compared to lobal Y-90 TARE, segmental Y-90 TARE treatment is preferred to lobar Y-90 TARE if segmental Y-90 TARE treatment is able to treat all blood supply to the predominant lesion or lesion with vascular invasion to preserve liver function. For segmental treatment, a minimum tumor dose of 190 Gy should be used for glass microspheres and 120 Gy for resin microspheres. For lobar treatment, a minimum dose of 100 Gy should be used for resin microspheres.

Arm A; Arm B

Atezolizumab DRUG

Atezolizumab 1200 mg will be delivered as an IV infusion on Day 1 of each cycle (every 3 weeks). The initial dose will be delivered over 60 (± 15) minutes and if tolerated subsequent infusions may be given over 30 minutes.

Also known as: Tecentriq

Arm B

Bevacizumab DRUG

Bevacizumab 15 mg/kg will be delivered as an IV infusion on Day 1 of each 3 week cycle.The initial dose will be delivered over 90 minutes (±15 minutes) and if tolerated subsequent infusions may be given over 60 minutes

Also known as: Avastin

Arm B

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Patients must be willing and able to provide written informed consent for this trial.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 at screening
• Histological or cytological evidence/confirmation per AJCC, 8th edition, of hepatocellular carcinoma (HCC).
• Measurable disease by RECIST 1.1.
• Patients must have at least Barcelona Clinic Liver Cancer (BCLC) stage B HCC and must be outside of Milan Criteria; and/or HCC peripheral vascular involvement of any size or number of tumor (segment peripheral, vp1 and vp2 are allowed, but vp3 and vp4 are excluded). NOTE: absence of extrahepatic spread, must be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) scan of the chest, abdomen, and pelvis.
• Patient must either (1) not be a candidate for liver transplantation as determined by the liver transplant service or (2) refuse evaluation for transplantation.
• Archival tissue obtained within 6 months of registration is required. If archival tissue is not available, subjects are not eligible.
• No prior systemic therapy is permitted. NOTE: Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound or TACE) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST 1.1. Prior TACE is allowed if FLR is ≥ 40%.
• Patient must be a TARE candidate, as defined by a lung dose threshold for Y-90 of 30Gy and an estimated (future liver remnants) FLR of ≥ 40% at the time of forming the comprehensive treatment plan. Both the lung dose threshold and FLR values must be obtained and available in source documentation.
• Patients must demonstrate adequate hepatic, bone marrow, and renal function as defined below. All screening labs should be performed within 14 days of treatment initiation.
• Hematological
• Lymphocyte Count: 500/μL
• Absolute Neutrophil Count (ANC): ≥ 1,500 /μL
• Hemoglobin (Hgb): ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment)

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Have signs of liver failure, e.g. clinically significant ascites, encephalopathy, or variceal bleeding within six months from enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX® are allowed.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding.
• Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment. 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 within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
• Have evidence of excessive hepatopulmonary shunting (\> 20% in 99mTc macro-aggregated albumin scan for resin and 30 Gy per treatment for glass) or angiographically demonstrable and non-occludable gastrointestinal shunting, precluding from Y-90 treatment.
• Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure \> 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. NOTE: Anti-hypertensive therapy to achieve these parameters is allowable.
• Prior history of hypertensive crisis or hypertensive encephalopathy.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Major surgery within 4 weeks prior to registration or anticipation of a major surgical procedure during study.
• Have had prior transplant of any kind (stem cell or solid organ).
• Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). 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.

Sponsors & Collaborators

• Aiwu Ruth He, MD: lead
• Georgetown University: collaborator
• Genentech, Inc.: collaborator

Study Sites (6)

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

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

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Aiwu R He, MD, PhD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 9, 2020
• Study Start: November 30, 2020
• Primary Completion: June 18, 2023
• Study Completion: June 30, 2023
• Last Updated: June 5, 2024
• Results First Posted: June 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)