Hepatocellular Carcinoma (HCC)
Conditions
Keywords
TARE, Durvalumab, Bevacizumab, Liver Cancer, Y90
Brief summary
The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC) amenable to embolization.
Detailed description
A Phase II single-arm study conducted in participants with unresectable Hepatocellular carcinoma (HCC) eligible for embolization and not eligible for or who have declined treatment with resection and/or ablation or liver transplant. Participants with previous Transarterial Chemoembolization (TACE) or TARE associated with the curative setting are permitted with a 6-month washout. Approximately 120 participants with unresectable but amenable to locoregional therapy HCC eligible for embolization will be screened in the study at approximately 20 sites in the US to enroll approximately 60 participants.
Interventions
DRUGDurvalumab
Durvalumab IV (intravenous)
DRUGBevacizumab
Bevacizumab IV (intravenous)
Yttrium 90 glass microspheres will be administered
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Participants with confirmed unresectable HCC * Participants with Lung dose threshold for Yttrium 90 glass microspheres of 30 Gy (equal or less than 30 Gy per treatment for glass) and an estimated Future liver remnant volume (FLRV) ≥ 30% of whole liver volume. * Participants with more than 1 prior embolization are permitted if more than 12 months ago, for a different primary lesion, and FLR \> 30%. * Participants with no evidence of extrahepatic disease on any available imaging * Participants with one or more measurable lesions, unilobar disease for participants with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2) and eligible for Yttrium 90 glass microspheres TARE. * Participants having Child-Pugh score class A. * Participants having ECOG performance status of 0 or 1 at enrollment * Adequate organ and marrow function
Exclusion criteria
* Disease amenable to curative surgery, ablation or transplantation. Transplant patients are considered eligible if outside of Milan criteria and not currently listed for transplant. * Participants co-infected with HBV and HDV * Any history of nephrotic or nephritic syndrome. * Clinically significant (eg, active) cardiovascular disease * Participants with uncontrolled hypertension * History of hepatic encephalopathy * Known hereditary predisposition to bleeding or thrombosis; any prior or current evidence of bleeding diathesis. * Receipt of more than 1 prior embolization (TACE or TARE) treatment/procedure * Participant has received any prior anticancer systemic therapy for unresectable HCC. * History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment. * History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From Day 1 until date of progressive disease or death [Approximately 3 years] | PFS is defined as the time from Day 1 (day of TARE) until the date of progressive disease per modified Response Evaluation Criteria in Solid Tumors (mRECIST), as assessed by the investigator, or death due to any cause. It is measured to assess the efficacy of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse events (AEs) | From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug | To assess the safety of the sequence of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy |
| Objective Response Rate (ORR) | From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years) | ORR is defined as the proportion of participants who have a confirmed complete response or partial response, as determined by the investigator per mRECIST. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy. |
| Overall Survival (OS) | Day 1 to 18 months or until death (Approximately 3 years) | OS is defined as the time from the start of TARE until the date of death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy. |
| Duration of Response (DoR) | Time from first documented response until documented progression (Approximately 3 years) | DoR is defined as the time from the date of first documented response (that is subsequently confirmed) until the date of documented progression per mRECIST as assessed by the investigator, or death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy. |
Countries
United States
Outcome results
None listed