None listed
Conditions
Interventions
Drug : Arm A (experimental arm):
- Atezolizumab 1200 mg intravenous (IV) infusions Q3W (dosed in 3-
week cycles) plus
- Bevacizumab 15 mg/kg IV Q3W (dosed in 3-week cycles)
Arm B (standard arm):
- Tr
Sponsors
IKF GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form available 2. Patients* = 18 years of age at time of signing Informed Consent Form (for Taiwan: = 20 years) 3. Confirmed hepatocellular carcinoma diagnosis based on histopathological findings from tumor tissue or typical diagnostic imaging on dynamic CT or MRI according to AASLD criteria. 4. Disease not amenable to curative surgery or transplantation or curative ablation BUT disease amenable to TACE 5. Extent of disease according to the following parameters: • Multifocal HCC beyond Milan criteria (i.e. >3 lesions of any size OR =ß lesions with at least one of them being = ?cm) • More than one untreated HCC untreated nodule > 10 mm showing arterial hyperenhancement • No massive multinodular pattern preventing adequate TACE • No tumor of a diffuse infiltrative HCC type • Patent portal vein flow • No portal vein invasion/thrombosis (even segmental) on baseline/eligibility imaging • No extrahepatic disease 6. Patients with recurrence after resection/ablation are eligible if initially having achieved complete response AND recurrence developed within ß years (i.e. =7?0 days) before trial inclusion AND if = ß untreated nodules with > 10 mm with arterial enhancement are present at timepoint of trial inclusion. 7. Child-Pugh score class A without ascites requiring more than 100 mg of spironolactone/day (see exclusion criteria) at enrollment. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 at enrollment. 9. Adequate organ and bone marrow function 10. Life expectancy of = ? months 11. The following laboratory values obtained less than or equal to 7 days prior to randomization. • Platelet count = 75,000 per µL (75x109/L) • Hemoglobin = 9.0 g per dL [transfusion allowed] • Total bilirubin = ß.0 x the upper limit of normal (ULN) • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 x ULN • Serum creatinine = 1.5 x ULN or creatinine clearance (CrCL) = 50mL/min (calculated using the Cockcroft-Gault formula) • Urine dipstick for proteinuria = 2+ (within 7 days prior to initiation of study treatment) Patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1 g of protein in 24 hours • INR or aPTT = 1.5 x ULN (therapeutic anticoagulation prohibited – see exclusion criterion #13; prophylactic anticoagulation permitted, e.g. LMW heparin, ASS up to 250mg/qd) • Alkaline phosphatase = ß.5 x ULN • Absolute neutrophil count (ANC) = 1.500 per µL (1.5x109/L) without granulocyte colony-stimulating factor support • Serum albumin = ß.8 g per dL (ß8g/L) 12. Pre-treatment tumor tissue sample (if available) • If tumor tissue is available, a formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or approximately 10 to 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report. • If FFPE specimens described above are not available, any type of specimens (including fine-needle aspiration, cell pellet specimens [e.g., from pleural effusion], and lavage samples) are also acceptable. This specimen should be accompanied by the associated pathology report. • If tumor tissue is not available (e.g., patient has never undergone biopsy or tissue depleted because of prior diagnostic testing), patients are still eligible. 13. Negative serum pregnancy test done lesser than or equal to 7 days prior to
Exclusion criteria
Exclusion criteria: 1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 2. Disease still amenable to curative surgery or transplantation or curative ablation. 3. Previous treatment with atezolizumab or bevacizumab. 4. Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of cancer immunotherapy for HCC. 5. Previous TACE or any other transarterial treatment for HCC • Previous RFA / MWA allowed (refer to inclusion criterion #6) • Other local therapies are prohibited (e.g. cryoablation, highintensity focused ultrasound, irreversible electroporation) 6. Extent of disease too advanced: • Evidence of macrovascular invasion (even segmental) on baseline / eligibility imaging • Massive multinodular pattern preventing adequate TACE • Extrahepatic disease 7. Tumor of diffuse infiltrative HCC type (hypovascular infiltrative tumors with ill-defined borders) 8. Clinically meaningful ascites, defined as ascites requiring nonpharmacologic intervention (e.g. paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. • Patients with ascites requiring pharmacologic intervention (e.g. diuretics) and stable for =ß months on low doses of diuretics (spironolactone 100 mg/d or equivalent) for ascites are eligible. Of note, diuretics for other indications such as congestive heart failure are not considered in this regard. 9. Previous radiotherapy for HCC 10. Major surgical procedure, open biopsy, or significant traumatic injury =ß8 days prior to randomization or anticipation of need for major surgical rocedure during the course of the study or non-recovery from side effects of any such procedure. 11. Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, as well as unstable arrhythmias (note: beta blockers or digoxin are permitted), unstable angina, new-onset angina (begun within the last 3 months). 12. Uncontrolled hypertension defined by a systolic blood pressure (BP) =150 mmHg or diastolic blood pressure (BP) =100 mmHg, with or without antihypertensive medication. Patients with initial blood pressure (BP) elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria. 13. Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. 14. History of or current pheochromocytoma. 15. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =6 months prior to randomization. 16. With regards to eligibility for adequate TACE, patients presenting with either of the following conditions are excluded: • Past history of bilioenteric anastomosis or biliary procedure (e.g., endoscopic papillotomy or biliary stenting) or patients with aerobilia • Central biliary obstruction (right or left intrahepatic duct, common hepatic duct, common bile duct) • Celiac occlusion 17. Ongoing infection > grade 2 NCI-CTCAE version 5.0. 18. Patients with seizure disorder requiring medication. 19. Prior allogeneic bone marrow transplantation or prior solid organ transpl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to failure of treatment strategy | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;Overall Survival Rate at 24 months;Objective Response Rate;Time to Progression;Time to loss of systemic treatment options;Progression free survival;Duration of Treatment;Duration of Response;Time to deterioration of liver function;Safety;Quality of Life | — |
Countries
Korea, Republic of
Contacts
Public ContactJeong Kim
P-pro korea
Outcome results
None listed