Health Condition 1: C220- Liver cell carcinoma
Conditions
Interventions
Intervention1: Durvalumab: Arm A: Durvalumab Q4W + DEB-TACE or cTACE. After completion of the last TACE procedure: Durvalumab + Bevacizumab Placebo (Q3W)
Control Intervention1: Bevacizumab: Arm B: Du
Sponsors
AstraZeneca AB
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age greater than or equal to 18 years at the time of screening. For patients aged lesser than 20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. 2. Confirmed HCC based on histopathological findings from tumor tissue 3. No evidence of extrahepatic disease on baseline chest/abdomen/pelvis imaging 4. Disease not amenable to curative surgery or transplantation or curative ablation 5. Disease must be amenable to TACE and anticipated to require no more than 4 TACE treatments to treat sites of disease within a lesser than or equal to 16 week period (Permitted modalities are DEB-TACE or cTACE (using an emulsion of Lipiodol® and a permitted chemotherapeutic agent as per institutional practice, followed by embolizing agents). 6. Child-Pugh score class A to B7 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment 8. Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and or or hepatitis B core antibodies (anti HBcAb) with detectable HBV DNA (greater than or equal to 10 IU per ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (HBV DNA lesser than or equal to 2000 IU per mL) prior to enrollment. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti hepatitis B core (HBc) with undetectable HBV DNA (lesser 10 IU per ml or under the limit of detection per local lab standard) do not require anti-viral therapy prior to enrollment. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (greater than or equal to 10 IU per ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. 9. Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti HCV antibody upon enrollment. 10. At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria Liver lesions that show typical features of HCC on IV contrast enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase Viable, non-necrotic portion (arterial phase IV contrast enhancing) that can be accurately measured at baseline as greater than or equal to 10 mm in the longest diameter 11. Adequate organ and marrow function as defined below. Criteria “a, ? “b, ? “c, ? and “f ? may not be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose. (a) Hemoglobin greater than or equal to 9.0 g per dL (b) Absolute neutrophil count greater than or equal to 1000 per µL (c) Platelet count greater than or equal to 75000 per µL (d) Total bilirubin lesser than or equal to 2.0 × the upper limit of normal (ULN) (e) alanine aminotransferase (ALT) and aspartate aminotransferase
Exclusion criteria
Exclusion criteria: 1. Any history of nephrotic or nephritic syndrome 2. Clinically significant (eg, active) cardiovascular disease, including Unstable angina within lesser than or equal to 6 months of randomization New York Heart Association Grade greater than or equal to 2 congestive heart failure Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG Peripheral vascular disease Grade greater than or equal to3 (eg, symptomatic and interfering with activities of daily living requiring repair or revision) Previous transient ischemic attack, or sub arachnoids hemorrhage within 6 months prior to randomization 3. Significant traumatic injury during 4 weeks prior to randomization 4. Known hereditary predisposition to bleeding or thrombosis any prior or current evidence of bleeding diathesis. 5. Systemic anticoagulation allowed, excluding Vitamin K antagonists 6. History of arterioembolic event including a stroke or myocardial infarctionhormonal therapy for non cancer related conditions (eg, hormone replacement therapy) is acceptable. 7. Non healing wound, active ulcer, or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require wound examinations every 3 weeks. 8. History of abdominal fistula or GI perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrolment 9. Patients who have had any kind of surgery in the past 28 days (diagnostic biopsy included) 10. Uncontrolled hypertension defined by a systolic pressure greater than 150 mmHg or diastolic pressure greater than 90 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. 11. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC 12. History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (no lactulose, rifaximin, etc, if used for purposes of hepatic encephalopathy) 13. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. Patients with ascites that has required pharmacologic intervention (eg, diuretics) and who have been on stable doses of diuretics for ascites for greater than or equal to 2 months are eligible. 14. Major portal vein thrombosis visible on baseline or eligibility imaging, patients with Vp3 and Vp4 are excluded 15. Patients with infiltrative type HCC 16. History of allogeneic organ transplantation 17. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of 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 Patients with vitiligo or alopecia <
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of Arm A compared with Arm CTimepoint: To assess the efficacy of Arm A compared with Arm C (Time frame-Approximately 4 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess disease-related symptoms, impacts, and HRQoL in patients treated in Arm A compared with Arm C as well as Arm B compared with Arm CTimepoint: - Time to deterioration in the following: i) EORTC QLQ-C30: Global health status/QoL, functioning (physical), multi-term symptom (fatigue), single-item symptom (nausea) ii) EORTC QLQ-HCC18: Single-item symptom (abdominal pain) - Symptoms, functioning, and global health status/QoL scale/item score analysis using EORTC QLQ-C30 and EORTC QLQ-HCC18 (Time frame-Approximately 4 years);To assess patient-reported overall change in health status and current state global impression of severity in Arm A compared with Arm C as well as Arm B compared with Arm CTimepoint: Patient global impression of change in health status and severity of cancer symptoms will be evaluated using PGIC and PGIS, respectively (Time frame-Approximately 4 years);To assess patient-reported treatment tolerability in Arm A compared with Arm C as well as Arm B compared with Arm CTimepoint: Collection of patient-reported outcomes version of the CTCAE (PRO-CTCAE) symptoms (Time frame-Approximately 4 years);To assess physician-reported patient outcome in patients treated in Arm A compared with Arm C as well as Arm B compared with Arm CTimepoint: Eastern Cooperative Oncology Group performance status (Time frame-Approximately 4 years);To assess the efficacy of Arm A compared with Arm C as well as Arm B compared with Arm CTimepoint: - Overall Survival (OS) - PFS using Investigator and BICR assessments according to mRECIST - ORR, DCR, DoR, and TTP using BICR assessments according to RECIST 1.1 - ORR, DCR, DoR, and TTP using Investigator and BICR assessments according to mRECIST - PFS2 per Investigator assessment as defined by local standard clinical practice (Time frame-Approximately 4 years);To assess the efficacy of Arm A compared with Arm C as well as Arm B compared with Arm C by PD-L1 expressionTimepoint: Association of PD-L1 expression level with: | — |
Countries
Australia, Brazil, Canada, China, France, India, Italy, Japan, Mexico, Republic of Korea, Spain, Taiwan, Thailand, United States of America, Viet Nam
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Limited
Outcome results
None listed