Sintilimab Plus Bevacizumab as Adjuvant Therapy in HCC Patients at High Risk of Recurrence After Curative Resection (DaDaLi)

A Phase III, Randomized, Open-lable, Multi Center Study of Sintilimab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Curative Hepatic Resection

This is an open label, multi-center, randomized, controlled phase III study, to evaluate the efficacy and safety of sintilimab plus bevacizumab as adjuvant therapy in hepatocellular carcinoma (HCC) patients who are at high risk of recurrence after radical resection

Study Overview

• Status: Not yet recruiting
• Conditions: HCC; Immunotherapy; Adjuvant Therapy
• Intervention / Treatment: Drug: Sintilimab; Drug: Bevacizumab

Detailed Description

There is no stardard adjuvant treatment for HCC. This study is to to evaluate the efficacy and safety of sintilimab plus bevacizumab as adjuvant therapy in HCC patients who are at high risk of recurrence after radical resection.

• Study Type: Interventional
• Enrollment (Anticipated): 246
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhongguo Zhou; Phone Number: 020-87343585; Email: 54757370@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a first diagnosis of HCC who have undergone a curative resection
• Radiologic evidence of disease free ≥4 weeks after complete surgical resection
• Full recovery from surgical resection or post-operative transarterial chemoembolization before randomization
• Randomization needs to occur within 12 weeks of the date of surgical resection
• High risk for HCC recurrence as protocol defined
• Child-Pugh Score, Class A
• ECOG performance status 0 or 1
• No prior systemic anticancer therapy for HCC
• Adequate hematologic and organ function

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC
• Evidence of residual, recurrent, or metastatic disease at randomization
• History of hepatic encephalopathy or organ transplantation
• Patients who are in the waiting list for liver transplantation
• Patients with Vp4 portal vein thrombosis
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or other immunotherapy
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; sintilimab 200mg + bevacizumab 7.5mg/kg IV Q3W	Drug: Sintilimab; Sintilimab 200mg IV Q3W; Other Names: Tyvyt; Drug: Bevacizumab; Bevacizumab 7.5mg/kg IV Q3W; Other Names: Byvasda
No Intervention: Arm B; Active surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival (RFS)	RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by the investigator, or death due to any cause (whichever occurs first).	up to 36 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS）	OS is defined as the time from the date of randomisation until death due to any cause	up to 48 months after randomization
RFS Rate at 12 and 24 months	RFS rate defined as the proportion of patients without recurrence or death from any cause at 12 and 24 months after randomization.	at 12 and 24 months after randomization
OS Rate at 24 and 36 Months	OS rate defined as the proportion of patients who have not experienced death from any cause at 24 and 36 months after randomization.	at 24 and 36 months after randomization
TTR(time to recurrence)	TTR is defined as the time the date of randomisation until first documented disease recurrence.	up to 36 months after randomization
Adverse Events (AEs)	The grade of AEs and the number of patients with AEs are assessed by the investigator based on CTCAE v5.0 from the date of randomization to 90 days after last dose of study treatment.	up to 48 months after randomization

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 20, 2020
• First Submitted That Met QC Criteria: December 20, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 20, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: B2020-280-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No