A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI CENTER STUDY OF DURVALUMAB MONOTHERAPY OR IN COMBINATION WITH BEVACIZUMAB AS ADJUVANT THERAPY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA WHO ARE AT HIGH RISK OF RECURRENCE AFTER CURATIVE HEPATIC RESECTION OR ABLATION (EMERALD-2)
- Conditions
- -C220 Liver cell carcinomaLiver cell carcinomaParoxysmal nocturnal haemoglobinuria [Marchiafava-Micheli]C220D595
- Registration Number
- PER-013-19
- Lead Sponsor
- AstraZeneca AB,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 0
1Provision of signed and dated written informed consent form (ICF) and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient/legal representative prior to any mandatory study-specific procedures, sampling, and analyses, including screening evaluations.
2Age ≥18 years at the time of screening. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
3Histologically or cytologically confirmed HCC and successfully completed curative therapy (resection or ablation).
(a)Hepatic resection and have the following pathologic findings from surgery:
(i)Any size with microvascular invasion (clear pathology assessment on microvascular invasion: Yes or No) or satellite tumor
(ii)3 or less tumors, with at least one >5 cm
(iii)4 or more tumors, ≤5 cm each
(b)Ablation (radiofrequency or microwave, cryoablation, or PEI per institutional standard) and have the following radiologic findings prior to ablation:
(i)Solitary tumor, 3 to 5 cm
(ii)2 to 4 tumors, ≤5 cm each
(iii)Exclude patients with 5 or more tumors.
4Patients must be randomized within 12 weeks after completion of curative hepatic resection or ablation.
5Imaging to confirm disease-free status within 28 days prior to randomization.
6Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 at enrollment.
7Child-Pugh score of 5 or 6.
8Patients with HBV infection (as characterized by positive hepatitis B virus surface antigen [HBsAg] and/or anti-hepatitis B core antibodies (HBcAbs) with detectable HBV deoxyribonucleic acid (DNA) [≥10 IU/mL or above the limit of detection per local laboratory]) must receive antiviral therapy at least after enrollment (sign of ICF) per institutional practice to ensure adequate viral suppression (HBV DNA ≤2000 IU/mL) prior to randomization. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment. Patients who test positive for anti HBcAb with undetectable HBV DNA (<10 IU/mL or under the limit of detection per local laboratory) do not require antiviral therapy. These patients will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/mL or above the limit of detection per local laboratory). Patients with detectable HBV DNA during the study must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study treatment.
1History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant”) during the 3 months prior to randomization.
2History of significant bleeding disorders, vasculitis, or a significant bleeding episode from the GI tract within 3 months prior to study randomization.
3History of GI perforation and/or fistulae within 6 months prior to randomization.
4Any history of nephrotic or nephritic syndrome.
5Evidence of symptomatic congestive heart failure (New York Heart Association II to IV) or symptomatic or poorly controlled cardiac arrhythmia.
6History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
7Uncontrolled arterial hypertension defined by a systolic pressure ≥150 mm Hg or diastolic pressure ≥90 mm Hg despite standard medical management.
8Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to randomization.
9Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
10Evidence of esophageal and/or gastric varices on upper endoscopy or contrast-enhanced cross-sectional imaging.
11Evidence of metastasis, macrovascular invasion, or co-existing malignant disease on baseline imaging.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Investigator tumor assessments will be performed using modified Response Evaluation Criteria in Solid Tumors (mRECIST 1.1) criteria.<br>Measure:Recurrence-free survival (RFS)<br>Timepoints:On-study tumor assessments (CT or MRI of the chest, abdomen, and pelvis) will occur Q12W (±1 week) following randomization for the first 24 months and then Q24W (±1 week) until Investigator-determined radiologic recurrence.<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Include OS; RFS, recurrence-free survival at 24 months (RFS24), recurrence-free survival at 36 months (RFS36), and time to recurrence (TTR) derived (by AstraZeneca) from BICR assessments according to RECIST 1.1; and time from randomization to recurrence/progression on the next therapy (RFS2/PFS2) as assessed by the Investigator according to local standard clinical practice.<br>Measure:Overall Survival OS; recurrence-free survival (RFS(, recurrence-free survival at 24 months (RFS24), recurrence-free survival at 36 months (RFS36), and time to recurrence (TTR)<br>Timepoints:Following completion or discontinuation of study treatment, assessments for survival must be made at Months 3, 6, and 9 (±1 week); Month 12 (±2 weeks); and then every 6 months (±2 weeks) thereafter.<br>