Health Condition 1: C220- Liver cell carcinoma
Conditions
Interventions
Intervention1: Durvalumab: Arm A: 1120 mg (Q3W) + Bevacizumab 15mg/kg (Q3W) for upto maximum of 12 months (18 doses or cycles)
Control Intervention1: Durvalumab Monotherapy or in Combination with Beva
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Provision 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 prior to any mandatory study-specific procedures, sampling, and analyses, including screening evaluations. 2. Age =18 years at the time of screening. . 3. Histologically or cytologically, newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation). a. Hepatic resection and have the following pathologic and/or radiologic findings from surgery: (i) Any size with microvascular invasion (clear pathologic 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. Embolisation (e.g. TACE/TAE) is acceptable so long as it is part of the local planned ablative process) where all curative procedures are completed within a 12 week window, 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. 4. Patients to be randomized within 12 weeks of completion of curative hepatic resection, or final curative ablation procedure. 5. Imaging confirmed disease-free status within 28 days prior to randomization. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 at enrollment. 7. Child-Pugh score of 5 or 6. 8. Patients 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 ( 9. Patients with HCV infection (as characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody) to be managed per local institutional practice for the study and for 6 months after the last dose of study treatment. 10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 month without alternative medical cause. The following age-specific requirements apply: 11. Women <50 years of age would be co
Exclusion criteria
Exclusion criteria: Medical conditions 1. History 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. 2. History of significant bleeding disorders, vasculitis, or a significant bleeding episode from the GI tract within 3 months prior to study randomization. 3. History of GI perforation and/or fistulae within 6 months prior to randomization. 4. Any history of nephrotic or nephritic syndrome. 5. Evidence of symptomatic congestive heart failure (New York Heart Association II to IV) or symptomatic or poorly controlled cardiac arrhythmia. 6. History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization. 7. Uncontrolled arterial hypertension defined by a systolic pressure =150 mm Hg or diastolic pressure =90 mm Hg despite standard medical management. 8. Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to randomization 9. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 10. Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging undertaken at the screening visit, or within 6 months (24 weeks) of randomization. 11. Evidence of distant metastasis (except regional lymph node metastases related to the disease under study, per Appendix F), co-existing malignant disease or macrovascular invasion on baseline imaging 12. History of hepatic encephalopathy within 12 months prior to randomization or requirement for medications to prevent or control encephalopathy (no lactulose, rifaximin, etc, if used for purposes of hepatic encephalopathy). 13. Evidence of portal vein thrombosis, visible on baseline/eligibility imaging, and patients with Vp1, Vp2, Vp3 and Vp4. 14. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first dose of study treatment. (Note:Patients with ascites who have required pharmacologic intervention (eg, diuretics) and who have been on stable doses of diuretics for ascites for =2 months before randomization are eligible) 15. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn s disease], diverticulitis [except for diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [eg, granulomatosis with polyangiitis, Graves disease, rheumatoid arthritis, hypophysitis, and uveitis]). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (eg, following Hashimoto syndrome), stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician e. Patients with celiac disease controlled by diet alone 16. Uncontrolled intercurrent i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of Arm B versus Arm CTimepoint: TRFS using BICR assessments according to RECIST 1.1 (Time frame-Approximately 2 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the efficacy of Arm A versus Arm CTimepoint: RFS using BICR assessments according to RECIST 1.1 (Time frame-Approximately 2 years);To assess the efficacy of Arm A versus Arm C and Arm B versus Arm CTimepoint: RFS (Recurrence Free Survival) at 24 months and TTR using BICR assessment according to RECIST 1.1 Overall survival at 36 months & Overall survival 48 months RFS2 PFS2 as assessed by the investigator according to local standard clinical practice ;To investigate the relationship between a patient baseline PDL-1 expression and efficacy outcome with Durvalumab by comparing Arm A versus Arm C and Arm B vs Arm CTimepoint: According to PDL-1 Expression level with the following • RFS at 24 months and TTR using BICR assessment according to RECIST 1.1 • Overall survival;To assess the efficacy of Arm A versus Arm C and Arm B versus Arm C by evidence of microvascular invasion (Yes vs No or Unknown) and geographic region (China vs [Asia without China and Japan] vs [Japan PLUS Rest of the world)Timepoint: RFS at 24 months and TTR using BICR assessment according to RECIST 1.1 • Overall survival;To investigate the immunogenicity of Arm A vs Arm BTimepoint: Presence of ADA for Durvalumab and Bevacizumab;To evaluate the population PK of Arm A vs Arm BTimepoint: Durvalumab and Bevacizumab concentration of PK parameters;To assess the disease related symptoms impacts, and HRQoL in patients treated in Arm A vs Arm C and Arm B vs Arm CTimepoint: EORTC-QLQ-30 and EORTC-QLQ HCC 18 time to deterioration in symptoms (abdominal pain , fatigue, appetite loss and nausea), functioning (eg physical) and global health status/QoL;Safety objective To assess the safety and tolerability of all treatment groupsTimepoint: AEs, physical examinations, vital signs, ECGs, and laboratory findings ECOG PS and Child PUGH Score;To collect blood and tissue sample for analysis of biomarkers and to explore potential biomarkers in residual biological sample that may influence the pro | — |
Countries
Australia, Austria, Brazil, Canada, China, France, Germany, Hong Kong, India, Italy, Japan, Peru, Philippines, Poland, Republic of Korea, Russian Federation, Taiwan, Thailand, Turkey, United States of America, Viet Nam
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd
Outcome results
None listed