Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment

Study Overview
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Brief Summary
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A global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab alone in patients with hepatocellular carcinoma who are at high risk of recurrence.

Detailed Description
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This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab monotherapy or placebo as adjuvant therapy. This study will be conducted in patients with HCC who are at high risk of recurrence after curative hepatic resection or ablation.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Bevacizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically (or radiologically for patients undergoing curative ablation), newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation) Imaging to confirm disease-free status within 28 days prior to randomization ECOG 0-1 at enrolment Child-Pugh score of 5 or 6 Adequate organ and marrow function. Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC Evidence of metastasis, macrovascular invasion or co-existing malignant disease on baseline imaging History of hepatic encephalopathy within 12 months prior to randomization Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging Patients with Vp1 to Vp4 portal vein thrombosis on baseline imaging are excluded Active co-infection with HBV and HDV. Receipt of prior systemic anticancer therapy for HCC Those on a waiting list for liver transplantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 150 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Durvalumab 1120 mg (Q3W) + bevacizumab 15 mg/kg (Q3W) | Drug: Durvalumab<br>* Durvalumab IV (intravenous)<br>* Other names: IMFINZI;Drug: Bevacizumab<br>* Bevacizumab IV (intravenous)<br>* Other names: AVASTIN;|
| Experimental: Arm B<br>Durvalumab 1120 mg (Q3W) + bevacizumab placebo (Q3W) | Drug: Durvalumab<br>* Durvalumab IV (intravenous)<br>* Other names: IMFINZI;Other: Placebo<br>* Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking<br>|
| Placebo Comparator: Arm C<br>Durvalumab placebo (Q3W) + bevacizumab placebo (Q3W) | Other: Placebo<br>* Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival (RFS) for Arm A vs Arm C | RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first. | Up to 49 months after first patient randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival (RFS) Arm B vs Arm C | RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first. | Up to 49 months after first patient randomized | 
| Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C | OS is defined as the time from the date of randomization until death due to any cause | No timeframe | 
| Recurrence-free survival at 24 months (RFS24) and 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C | Proportion of RFS at 24 months and at 36 months | At 24 and at 36 months | 
| Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C | TTR is defined as the time from the date of randomization until the date of disease recurrence | Up to 49 months after first patient randomized | 
| Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C | Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) | Up to 49 months after first patient randomized | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Durvalumab, Early stage HCC, Bevacizumab, Liver Cancer