None listed
Conditions
Brief summary
This study will investigate the effect Atezolizumab (Anti-PD-L1 Antibody) Plus Bevacizumab (Anti-VEGF Antibody) Immunotherapy Before Surgical Resection Versus Surgical Resection alone in Hepatocellular Carcinoma Patients Who is it for? You may be eligible to join this study if you are aged 18 years or above and have a first diagnosis of hepatocellular carcinoma and a recommendation of curative resection. Study details Participants in this study will be randomly allocated (by chance) to one of two groups: one group will receive immunotherapy of atezolizumab (Tecentriq) and bevacizumab (Avastin) followed (within a few days of receiving the second cycle of immunotherapy) by surgical resection and will be followed up with active surveillance every 3 months for 3 years. The other group will receive surgical resection only with active surveillance every 3 months for 3 years. Active surveillance will involve MRI/CT scans and blood tests. It is hoped this research will improve outcomes for patients with early-stage Hepatocellular Carcinoma by reducing the risk of disease recurrence.
Interventions
Interventional arm: Treatment of early-stage hepatocellular carcinoma with neoadjuvant immunotherapeutic agents atezolizumab (Tecentriq) and bevacizumab (Avastin) followed by surgical resection with active surveillance in patients with high onco-fetal characteristics.
Patients will be tested for onco-fetal characteristics (high onco-fetal score, determined as >10% onco-fetal cells and/or high Glypican-3, determined as positive staining in >10% cells and/or alpha fetoprotein (AFP) >400 ng/mL). P
Interventional arm: Treatment of early-stage hepatocellular carcinoma with neoadjuvant immunotherapeutic agents atezolizumab (Tecentriq) and bevacizumab (Avastin) followed by surgical resection with active surveillance in patients with high onco-fetal characteristics. Patients will be tested for onco-fetal characteristics (high onco-fetal score, determined as >10% onco-fetal cells and/or high Glypican-3, determined as positive staining in >10% cells and/or alpha fetoprotein (AFP) >400 ng/mL). Patients with high onco-fetal characteristics will be randomised 1:1 into intervention and control arms. Patients with low onco-fetal score will receive control treatment only. Intervention Regime: Participants will receive 2 cycles of immunotherapy in total, 3 weeks apart, as follows: Cycle 1: Day 0 - Atezolizumab will be administered by intravenous infusion at a fixed dose of 1200 mg and Bevacizumab will be administered intravenous infusion at a dose of 15 mg/kg. Cyle 2: Day 21 - Atezolizumab will be administered by intravenous infusion at a fixed dose of 1200 mg as monotherapy. Day 22-23 - Surgical resection Patients will be followed up every 3 months for 3 years following surgery. Details of all treatments and follow up assessments will be recorded in patient medical records.
Sponsors
Western Sydney Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Signed Informed Consent Form - Age greater than or equal to 18 years - Ability to comply with the study protocol - First diagnosis of HCC and MDT recommendation of curative resection - Absence of major macrovascular invasion - Absence of extrahepatic spread - AST and ALT less that or equal to 5 × upper limit of normal (ULN) and total bilirubin less than or equal to 51 µmol/L - Baseline FFPE tumour tissue biopsy - Documented virology status of hepatitis B and C - ECOG Performance Status of 0 or 1 - Child-Pugh Class A status or up to B7 - Adequate hematologic and end-organ function
Exclusion criteria
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC - Evidence of residual, recurrent, or metastatic disease - Clinically significant ascites - History of hepatic encephalopathy - Prior bleeding event due to untreated or incompletely treated oesophageal and/or gastric varices - Active or history of autoimmune disease or immune deficiency - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Significant cardiovascular disease - History of malignancy other than HCC within 5 years prior to screening - Active tuberculosis - Severe infection within 4 weeks prior to treatment - Prior allogeneic stem cell or solid organ transplantation - On the waiting list for liver transplantation - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications - Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab - Women of childbearing potential without a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle 1 - Co-infection with HBV and hepatitis D viral infection - Clinically significant hypercalcemia - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins - Hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulations - Any prior treatment for HCC - History of hypertensive crisis or hypertensive encephalopathy - Significant vascular disease - History of hemoptysis - Evidence of bleeding diathesis or significant coagulopathy - History of GI fistula, GI perforation, or intra-abdominal abscess within 6 months prior to treatment - Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture - Major surgical procedure within 4 weeks prior to treatment
Outcome results
None listed