In this phase 2 study, the investigators aim to evaluate the effects and safety of combined therapy using oxaliplatin and gemcitabine chemotherapy, Donafenib and Tislelizumab for patients with advanced biliary tract carcinoma.
Most advanced biliary tract carcinoma (BTC) patients are often accompanied by local or distant metastases and lose the opportunity for surgical resection. For patients with advanced BTC who have been in stages III and IV (AJCC/UICC, V2, 2018), the survival time is less than 4 months, and there is currently no standard treatment. The Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced BTC, but the efficacy is still unsatisfactory. Donafenib is a small molecule multi-kinase inhibitor, the main targets including VEGFR1-3, PDGFRα, RET(ret proto-oncogene ), c-KIT(KIT proto-oncogene, receptor tyrosine kinase), Raf,FLT3,have anti-angiogenic effects, have been proven effective in hepatocellular carcinoma. In recent years, monoclonal antibodies against programmed cell death protein 1 (PD1) have shown remarkable therapeutic effects in the treatment of various solid tumors. Prior to this, the combined treatment of GEMOX combined with Donafenib and Tislelizumab was proved satisfying safety. Meanwhile,the phase-I trial showed good efficacy in conversion rate and 6-month overall survival rate. Due to the limitted small sample size of the phase I trial, the investigators aim to expand the sample size to further verify the effects and safety of combined therapy in the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
93
Combination of Gemcitabine, Oxaliplatin, Donafenib and Tislelizumab every 3 weeks
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGOverall response rate
objective response rate(ORR),defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1
Time frame: 6 months
1-year Recurrence free survival
1-year Recurrence free survival
Time frame: 1 year
Progression-free survival
progression-free survival(PFS), defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator
Time frame: 6 months
Overall survival
overall survival(OS), defined as the time from enrollment to death due to any cause.
Time frame: 6 months
Incidence and degree of Adverse Events and Serious Adverse Events
Incidence, severity, and relationship to study drugs of all adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).
Time frame: 6 months
Conversion rate
Conversion rate, defined as the percentage of the conversion of patients with BTC assessed as unresectable into resectable through interventions, including the conversion of unresectable into resectable in the scientific sense such as insufficient future liver remnant(FLR), as well as the conversion of R1 and R2 to R0.
Time frame: 6 months
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