Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular Carcinoma, Donafenib, Sintilimab, TKI, PD-1 inhibitor
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.
Interventions
DRUGDonafenib+sintilimab
Part 1 (Safety Run-in): donafenib 200mg P.O. BID and sintilimab 200mg I.V. for a 21-days cycle. Part 2: 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.
Sponsors
Second Affiliated Hospital of Guangzhou Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) assessed by investigators according to modified Response Evalutaion Criteria in Solid Tumors (mRECIST). | 18 months | The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by investigators according to Response Evalutaion Criteria in Solid Tumors (RECIST) v1.1 | 18 months | The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first. |
| Objective response rate (ORR) assessed by investigators according to mRECIST. | 18 months | The percentage of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR). |
| Adverse Events (AEs) | 18 months | Number of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0. |
| ORR assessed by investigators according to RECIST 1.1. | 18 months | The percentage of patients who had a best overall tumor response rating of CR or PR. |
| DCR assessed by investigators according to RECIST 1.1. | 18 months | The percentage of patients who had a tumor response rating of CR, PR, or SD. |
| Disease control rate (DCR) assessed by investigators according to mRECIST. | 18 months | The percentage of patients who had a tumor response rating of CR, PR, or stable disease (SD). |
Countries
China
Outcome results
None listed