This trial is to evaluate the efficacy of Gemcitabine-Cisplatin (GC) plus Envafolimab neoadjuvant therapy in the patients at high risk of recurrence. Primary endpoint: Major Pathologic Response (MPR). It will also learn about the safety of drug including Gemcitabine-Cisplatin (GC) plus Envafolimab as a neoadjuvant therapy in this trial.
This trial is a single-arm interventional clinical study to evaluate the efficacy and safety of neoadjuvant gemcitabine-cisplatin plus Envafolimab in resectable biliary tract malignancies patients with high-risk of recurrence. Patients with high-risk factors for recurrence. The criteria were defined as meeting at least one of the following: a. Preoperative CA19-9 ≥ 200 U/mL; b. Tumor diameter ≥5 cm or multiple tumor nodules on imaging; c. Regional lymph node metastasis with a short-axis diameter ≥ 1.0 cm on imaging; d. Vascular invasion (portal vein or hepatic artery) on imaging; e. Low or undifferentiated histologic grade. The primary endpoint: Major Pathologic Response (MPR). Secondary endpoints: Overall Survival (OS), Disease-free survival (DFS), Objective Response Rate (ORR) per the Response Evaluation Criteria In Solid Tumors (RECIST v1.1), Pathologic Response Rate (PCR), and R0 resection rate. The incidence and severity of adverse events (AEs), serious adverse events (SAEs), and laboratory test abnormalities judged as per the CTCAE v5.0 criteria. Exploratory endpoint: Relationship between carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), Pathological biomarker expression, spatial transcriptome (if samples are sufficient), gut microbiome metagenome sequencing, and treatment response.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
First: Envafolimab: 400 mg on Day 1, repeated every 3 weeks (Q3W). GC chemotherapy: Gemcitabine: 1000 mg/m2 in 100 mL of 0.9% sodium chloride injection, administered intravenously over 30 minutes on Days 1 and 8, repeated Q3W. Cisplatin: 25 mg/m2 in 500 mL of 5% glucose injection, administered intravenously over 2 hours on Day 1 and 8, repeated Q3W. Of note, no target drugs is involved. Second: Radical resection eligibility will be assessed by the investigator; those with indeterminate resectability require additional MDT discussion confirmation. The criteria for radical resection: 1. No invasion of the main trunk of the hepatic vein, portal vein, or inferior vena cava; 2. No distant metastasis except for hilar lymph node metastases; 3. Minimum distance between surgical margin and tumor border ≥ 0.5 cm; 4. Residual liver volume ≥ 30% (≥ 40% for participants with cirrhosis).
Major Pathologic Response (MPR)
MPR is defined as ≤10% residual viable tumor cells in the primary lesion and regional lymph nodes following neoadjuvant therapy, with Pathologic Response Rate (PCR, 0% viable tumor cells) included in the MPR definition.
Time frame: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.
Residual viable tumor cell ratio
Postoperative resected specimens are analyzed via pathological section to determine the residual viable tumor cell ratio
Time frame: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.
Objective Response Rate (ORR)
ORR is defined as the sum of Complete Response (CR) and Partial Response (PR), representing the proportion of participants with sustained tumor regression meeting predefined criteria.
Time frame: From enrollment until 2-4 weeks after completion of neoadjuvant therapy (three cycles, each cycle is 21 days)
Pathologic Response Rate (PCR)
No viable tumor cells are found in the review of pathological sections.
Time frame: From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.
R0 resection
R0 resection rate refers to the proportion of patients achieving complete surgical resection with negative margins.
Time frame: From enrollment to 2-4 weeks after completion of thrid cycles (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.
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Overall Survival (OS)
OS is defined as the time from participant receiving the first treatment until death from any cause.
Time frame: From enrollment up to 2 years following treatment initiation
Disease-free survival (DFS)
DFS is defined as the time from the date of surgery to neoplasm recurrence or death for participants without residual lesions after surgery, whichever occurs first.
Time frame: From enrollment up to 2 years following treatment initiation