Clinical trial NCT05162352: Donafenib Plus Sintilimab for Advanced HCC
Official title: Donafenib Combined With Sintilimab for Advanced HCC: a Single-arm, Single-center, Prospective Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Donafenib
Sintilimab
TKI
PD-1 inhibitor
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2021-12-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of donafenib combined with sintilimab in patients with advanced hepatocellullar carcinoma (HCC).

Detailed description: This is a Phase II study to evaluate the efficacy and safety of donafenib combined with sintilimab in patients with advanced HCC.

30 subjects with advanced HCC (Barcelona-Clinic- Liver-Cancer \[BCLC\] stage C, or China liver cancer staging \[CNLC\] IIIa/IIIb) will be enrolled in the study.

Part 1 (Safety Run-in): 6 patients will receive donafenib 200mg P.O. BID and sintilimab 200mg I.V. for a 21-day cycle.

Part 2: patients will receive donafenib at the recommended phase 2 dose determined from Part 1 and sintilimab 200mg I.V. Q3W.

Donafenib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sintilimab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Patients will be allowed to have donafenib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

Eligibility criteria: Inclusion Criteria:

* Advanced HCC (BCLC stage C or CNLC IIIa/IIIb ) with diagnosis confirmed by histology/cytology or clinically
* Patients who have Tumor recurrence after surgical resection or ablation are allowed to be included
* Patients who previously received local treatment, such as transcatheter arterial chemoembolization, transcatheter arterial embolization and radiotherapy, are allowed to be included
* At least one measurable lesion
* Child-Pugh score ≤7
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ and hematologic function
* Life expectancy of at least 3 months

Exclusion Criteria:

* Diffuse HCC
* Macrovascular invasion involving the main trunk or inferior vena cava
* Central nervous system metastasis
* History of malignancy other than HCC
* Esophageal and/or gastric varices bleeding within 3 months prior to initiation of study treatment
* Uncontrolled ascites
* History of hepatic encephalopathy
* Patients who received prior systemic therapy (chemotherapy, targeted therapy or immunotherapy) or hepatic arterial infusion chemotherapy (HAIC) for HCC
* History of organ and cell transplantation
* Active severe infection; use of antibiotics within 2 weeks prior to injection of sintilimab
* Autoimmune disease or immune deficiency
* Severe organ (heart, kidney) dysfunction

Primary outcomes:
measure: Progression free survival (PFS) assessed by investigators according to modified Response Evalutaion Criteria in Solid Tumors (mRECIST).
timeFrame: 18 months
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: 18 months
measure: PFS assessed by investigators according to Response Evalutaion Criteria in Solid Tumors (RECIST) v1.1
timeFrame: 18 months
measure: Objective response rate (ORR) assessed by investigators according to mRECIST.
timeFrame: 18 months
measure: Disease control rate (DCR) assessed by investigators according to mRECIST.
timeFrame: 18 months
measure: ORR assessed by investigators according to RECIST 1.1.
timeFrame: 18 months
measure: DCR assessed by investigators according to RECIST 1.1.
timeFrame: 18 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Kangshun Zhu, Dr.
role: PRINCIPAL_INVESTIGATOR
References: