Resectable Hepatocellular Carcinoma With High Risk of Recurrence
Conditions
Keywords
Hepatocellular Carcinoma, Neoadjuvant therapy, TACE, Atezolizumab
Brief summary
This is an open-label, single-arm, multicenter, prospective, phase II clinical study to evaluate the efficacy and safety of TACE combined with Atezolizumab and Bevacizumab as neoadjuvant treatment in Hepatocellular Carcinoma.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
DRUGBevacizumab
Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle.
TACE will be performed by clinical demand.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed Informed Consent Form available 2. Patients ≥ 18 years and ≤75years of age at time of signing Informed Consent Form 3. Diagnosis of HCC confirmed by histology 4. Initially resectable with high-risk recurrence factors. High-risk features for resected patients include tumor size \>5 cm, tumor number \>3, vascular invasion (microvascular invasion or macrovascular invasion - Vp1/Vp2 - of the portal vein) and poor tumor differentiation (defined as Grade 3 or 4). Up to three tumors, with largest tumor \>5 cm regardless of vascular invasion (microvascular invasion or macrovascular invasion of Vp1/Vp2) or poor tumor differentiation (Grade 3 or 4) Four or more tumors, with largest tumor ≤5 cm regardless of vascular invasion (microvascular invasion or macrovascular invasion of Vp1/Vp2) or poor tumor differentiation (Grade 3 or 4) Up to three tumors, with largest tumor ≤5 cm with vascular invasion (microvascular invasion or macrovascular invasion of Vp1/Vp2) and/or poor tumor differentiation (Grade 3 or 4) 5. Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator 6. Child-Pugh A 7. ECOG PS 0～1 8. No prior locoregional or systemic treatment for HCC 9. Negative HIV test at screening
Exclusion criteria
1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma, recurrent HCC and diffuse HCC 2. Clinically diagnosed hepatic encephalopathy in the last 6 months 3. Autoimmune hepatitis (requiring liver puncture) 4. History of organ transplantation 5. Clinical symptoms of pleural effusion, ascites, pericardial effusion, and any history of kidney disease or nephrotic syndrome 6. Treatment with investigational therapy within 28 days prior to initiation of study treatment 7. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding 8. A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment 9. Known severe allergic reaction to contrast (e.g., anaphylaxis). 10. Pregnancy or lactating women. 11. Inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | At the time of surgery | pCR rate is defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response (MPR) Rate | At the time of surgery | MPR rate is defined as the proportion of participants with =\<30% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review. |
| Relapse-Free Survival (RFS) | Surgery to the first documented recurrence of disease (up to approximately 2 years) | RFS is defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic) according to EASL and/or RECIST v1.1, or death from any cause. |
| Event-Free Survival (EFS) | Enrollment up to approximately 2 years | EFS is defined as the time from enrollment to any of the following events (whichever occurs first): disease progression that precludes surgery, as assessed by the investigator according RECIST v1.1; local regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause. |
| Overall Survival (OS) | Enrollment to death from any cause (up to approximately 5 years) | OS is defined as the time from enrollment to death from any cause. |
| Treatment-related and -unrelated toxicities (AEs, SAEs) according to NCI CTCAE v5.0 | From the start of treatment to 30 days after surgery | Summary of adverse events by treatment arm and CTCAE (version 5.0) grade and frequency of clinically significant abnormal laboratory parameters. |
Countries
China
Contacts
Primary ContactXinyu Bi
Backup ContactXiaowu Zhang
Outcome results
None listed