This phase II trial studies how well gemcitabine, cisplatin and durvalumab/Pembrolizumab and surufatinib work in treating participants with advanced Biliary Tract Cancer. The international multicenter phase III clinical study TOPAZ-1 has confirmed that durvalumab combined with gemcitabine and cisplatin can bring survival benefits to advanced BTC. Whether if adding surufatinib to a standard of care can bring addition benefit needs to be explored.
Patients with biliary tract cancer who are clearly diagnosed by pathology, are unable to undergo radical surgery or have local/distant metastasis (allowing surgical treatment after successful transformation).
Have at least 1 lesion that can be measured according to RECIST v1.1 (more than 1cm on CT or MRI).
Have not received systematic anti-tumor therapy before.
Expected survival greater than 3 months;
Join another clinical study at the same time, unless it is during the follow-up period of an observational (non-interventional) or supportive care clinical study or interventional study.
Obstructive jaundice (bilirubin > 1.5 ULN) with inadequate biliary drainage.
Absolute neutrophil count (ANC) <1×109/L or platelet <80×109/L or hemoglobin < 8g/dL (based on the normal value of the clinical trial center)
Serum total bilirubin was 5 times higher than the upper limit of the normal reference range;
Single group
Surufatinib
Drug200mg，qd，po
Gemcitabine
Drug1000mg/ m2, IV，d1，8，q3w
Cisplatin
Drug25mg/m2，IV，d1，8，q3w
Durvalumab
Drug1500mg，IV，d1，q3w
Pembrolizumab
Drug200mg，IV，d1，q3w
ORR
Disease assessments based on investigator assessments were determined by using RECIST version 1.1 guidelines. The ORR was defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions. The PR was defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR was defined as 2 CRs or 2 PRs with no evidence of progression in-between. Patients who discontinued randomized treatment without progression, received a subsequent anti-cancer therapy and then responded were not included as responders for ORR.
PFS
PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of treatment until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
OS
Overall Survival (OS) was defined as the time from the date of treatment until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
conversion rate
Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection or transplantation after successful down-sizing of tumor(s) by intervention.
safety
Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI CTCAE 5.0)
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Dai, Guanghai
Lead sponsor
Chinese PLA General Hospital
Sponsor institution
