Hepatocellular Carcinoma
Conditions
Keywords
Immune re-challenge for HCC
Brief summary
The purpose of this study is to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma
Detailed description
Jak inhibitors have already demonstrated the ability to reverse T-cell exhaustion in the treatment of Hodgkin lymphoma. Gecacitinib is a Jak inhibitor that has been approved for the treatment of bone marrow fibrosis. This study was designed to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma . Total 35 subjects will be recruited in this study, ORR will be will be used as primary outcome measures, OS, PFS, DCR and safety will be the secondary endpoints.
Interventions
DRUGGecacitinib Combined With Donafenib and PD-1 Inhibitor
Subjects were enrolled and started receiving treatment with Gecacitinib (100mg, Bid, po) for 7 consecutive days; thereafter, they were treated with PD-1 antibody (Q3W, iv) and Donafenib (200mg, Bid, po), counting the day of infusion of PD-1 monoclonal antibodies as C1D1, with each cycle lasting 3 weeks. Subsequent treatments involved administering Gecacitinib for 1 week before each infusion of PD-1.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age and gender: \>18 years old and≤75 years old, both men and women. 2. All subjects must have Hepatocellular Carcinoma confirmed by pathological or clinical diagnosis. 3. Patients with viable and measurable target lesion per RECIST 1.1. 4. Patients with unresectable hepatocellular carcinoma (uHCC) who experienced disease progression after first-line therapy containing immune checkpoint inhibitors. 5. Patients who are expected to live more than 3 months. 9.ECOG PS 0-1. 10.Child-Pugh ≤7.
Exclusion criteria
1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology. 2. History of malignant tumor, excluding the following cases: 1. Malignant tumor that was curatively treated more than 5 years prior to study entry and has not recurred since then; 2. Successful radical resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, preinvasive cervix carcinoma, and other preinvasive cancers. 3. Diffuse tumor lesion. 4. Preexisting or history of hepatic encephalopathy, hepatorenal syndrome or liver transplantation. 5. Clinically uncontrolled ascites or pleural effusion. 6. Received treatment with a JAK inhibitor previously . 7. Clinically severe gastrointestinal bleeding within 6 months of the start of treatment or any life-threatening bleeding events within 3 months of the start of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | Evaluation of tumor burden based on mRECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | From date of enrollment until the date of death from any cause, assessed up to 3 years | — |
| PFS | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | Evaluation of tumor burden based on mRECIST criteria |
| DCR | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | Evaluation of tumor burden based on mRECIST criteria |
| Incidence of treatment-related adverse events (TRAE) | From date of enrollment until the date of 30 days after the last treatment according to the protocol, assessed up to 3 years | Number of patients with AE, treatment-related AE (TRAE), serious adverse event (SAE) assessed by CTCAE v5.0 |
Countries
China
Contacts
Primary ContactWei Zhang
Outcome results
None listed