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

Recruiting now · Phase 4

Conditions studied: Hepatocellular Carcinoma, Hepatocellular Cancer

In brief

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.

Key facts

Study ID

NCT05185505

Run by

The Methodist Hospital Research Institute

People needed

24

Starts

2023-01-30

Expected to finish

2027-10-31

Last updated by the study team

2023-02-01

Who can join

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

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)
• Aspartate transaminase (AST),alanine aminotransferase (ALT), and alkaline phosphatase (ALP) < 2.5 x ULN
• Serum albumin > 2.7 g/dL
• Serum creatinine < 1.5x ULN or calculated creatinine clearance < 50 ml/min
• Urine dipstick for proteinuria ≥ 2+ unless a 24-hour urine protein < 1 g of protein is demonstrated
• International normalized ratio (INR) ≤ 1.5 or partial thromboplastin time (PTT) ≤ 1.5 x ULN for patients not receiving anti-coagulation. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or PTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the first study treatment.
• No evidence of a Grade 2 or higher esophageal and/or gastric varices. Patients must have an esophagogastroduodenoscopy (EGD) within 6 months prior to initiating the study treatment. See Section 8.7.1.2.
• No history of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
• Negative HIV test at screening or transplant workup
• Negative hepatitis B surface antigen (HBsAg) test at screening or transplant workup
• Negative total hepatitis B core antibody (HBcAb) test at screening or transplant workup, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening or transplant workup. The HBV DNA test will be performed only for patients who have a negative HBsAg test and a positive total HBcAb test.

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
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. 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 prior to initiating the study treatment do not need to repeat the procedure.
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Other malignancy within 5 years prior to randomization, except for localized cancer in situ, such as basal or squamous cell skin cancer
• Current or recent (<10 days prior to initiation of study treatment) use of aspirin (>325 mg/day), or clopidogrel (>75 mg/day). Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or a PTT is within therapeutic limits (according to institution standards) within 14 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk.
• Pregnancy (positive pregnancy test) or lactation, or intention of becoming pregnant during study treatment or within 6 months after the final dose of study drugs
• o Women of childbearing potential must have a negative serum or urine pregnancy test result within 28 days prior to initiation of study treatment.
• 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
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
• 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:

Where it is running

• Houston Methodist Research Institute — Houston, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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