Atezolizumab and Bevacizumab Pre-Liver Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria

NCT05185505 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: PRO00032239ML43352
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are transplant-eligible will be treated with 6 months of neoadjuvant/downstaging atezolizumab plus bevacizumab while receiving standard of care transarterial chemoembolization (TACE). We hypothesize that atezolizumab and bevacizumab can appropriately bridge patients with HCC beyond MC to transplantation and not increase the risk of 1-year post-transplant rejection.

Conditions

Hepatocellular Carcinoma; Hepatocellular Cancer

Keywords

Bevacizumab; atezolizumab; Neoadjuvant Therapy; Liver Neoplasms; Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Receiving Liver Transplant Experiencing Acute Rejection

  The proportion of liver transplant patients who have acute allograft rejection

  Within 1 year after liver transplant

Secondary Outcomes (9)

• Proportion of participants who experience treatment-emergent adverse events

  Within 90 days of study drug administration

• Objective Response Rate

  6 months post study drug initiation

• Proportion of participants who are removed from the liver transplant waiting list after initiating the atezolizumab/bevacizumab therapy

  Through study completion, up to 4 years

• The proportion of participants who proceed to liver transplantation

  Through study completion, up to 4 years

• Proportion of the liver explant tissue containing necrotic tumors

  Through study completion, up to 4 years

Study Arms (1)

Atezolizumab + Bevacizumab

EXPERIMENTAL

Patients will receive transarterial chemoembolization (TACE) every 3 months, with a maximum of 4 treatments, plus atezolizumab combined with bevacizumab.

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

1200 mg administered every three weeks for up to 6 months (up to 8 cycles) during the liver transplant waiting period

Also known as: Tecentriq

Atezolizumab + Bevacizumab

Bevacizumab DRUG

15 mg/kg administered every three weeks for up to 6 months (up to 8 cycles) during the liver transplant waiting period

Also known as: Avastin

Atezolizumab + Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Male or female, aged ≥18 years old at the time of signing Informed Consent Form
• Measurable or evaluable disease per RECIST v1.1 or mRECIST of unresectable HCC outside of Milan criteria
• Histologically proven HCC, without extrahepatic disease. Patients who consent to a fresh tissue biopsy, and under the discretion of the Investigators, will provide a baseline biopsy sample for diagnosis and correlative studies. Archival tumor tissue may be used to confirm HCC in patients who do not consent to a fresh tissue biopsy.
• Prior remote LRT is allowed if new lesions or local disease recurrence are present
• Must be eligible for liver transplantation, defined in Section 10.4
• Eligible and suited to receive TACE procedure(s)
• Child-Pugh score ≤A6
• Eastern Cooperative Oncology Group (ECOG) score 0-1
• Life expectancy of ≥ 6 months
• Adequate hematological and end-organ function, defined by the following laboratory test results obtained within 14 days prior to study initiation:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Lymphocyte count ≥ 0.5 x 10\^9/L (500/uL)
• Platelet count \> 75 x 109/L
• Hemoglobin \> 9 g/dL
• Total bilirubin \< 1.5 x upper limit of normal (ULN)

You may not qualify if:

• Known fibrolamellar HCC, sacromatoid HCC, or mixed cholangiocarcinoma and HCC
• Previous systemic therapy for HCC prior to study enrollment
• Planned or prior multi-organ transplant or prior solid organ or allogeneic stem cell transplantation
• History of Grade ≥4 venous thromboembolism
• History or evidence upon physical or neurological examination of central nervous system (eg seizures) unrelated to cancer unless adequately treated with standard medical therapy. Anticonvulsants (stable dose) are allowed.
• Moderate or severe ascites
• History of hepatic encephalopathy
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg)
• History of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to drug administration
• 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
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to initiation of study treatment, or anticipation of need for major surgical procedure during the Treatment Phase of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to initiation of study treatment. Placement of a vascular access device should be at least 2 days prior to initiation of study treatment.
• History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, grade 2 or higher untreated esophageal or gastric varices or active GI bleeding within 6 months prior to treatment

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Houston Methodist Research Institute

Houston, Texas, 77030, United States

RECRUITING

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Related Links

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• McClain KL;., O. E. Clinical Features and Diagnosis of Hemophagocytic Lymphohistiocytosis.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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

Central Study Contacts

Darrel Cleere, BSN

CONTACT

713-441-6232; dwcleere@houstonmethodist.org

Shondra Word

CONTACT

713-441-5122; sword@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine in Oncology, Houston Methodist Academic Institute

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: January 11, 2022
• Study Start: January 30, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)