Biliary Tract Cancer
Conditions
Keywords
Resectable Biliary Tract Cancer, High Risk of Recurrence
Brief summary
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.
Detailed description
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.
Interventions
DRUGNeoadjuvant therapy followed by surgery
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).
Sponsors
Sir Run Run Shaw Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The detailed schedule for each cycle is as follows: 1) Envafolimab: 400 mg on Day 1, repeated every 3 weeks (Q3W). 2) 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have signed a written Informed Consent Form (ICF); * Male or female participants aged 18-80 years; * Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0/1; * Biliary Tract Cancer (BTC) diagnosed by puncture pathology prior to enrollment; * Participants must meet the following requirements for major vital organ function: a. Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 90×10⁹/L; hemoglobin ≥ 9 g/dL; b. Coagulation function: international normalized ratio (INR) ≤ 1.2; c. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 times the upper limit of normal (ULN); d. Serum albumin ≥ 3.5 g/dL; total bilirubin ≤ 1.5 times the ULN. Patients with obstructive jaundice who meet the eligibility criteria after percutaneous transhepatic cholangial drainage or endoscopic retrograde cholangiopancreatography treatment are also eligible for enrollment; e. Child-Pugh class A or B; f. Serum creatinine ≤ 1.5 times the ULN; * Patients with high-risk factors for recurrence. The criteria are 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; * Participants who have at least 1 measurable lesion (RECIST v1.1); * Be able to provide fresh stool samples and liver samples if undergoing surgery.
Exclusion criteria
* Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma, and other non-cholangiocarcinoma malignant tumor components; * Prior systemic therapy for BTC, including immunotherapy, targeted therapy, or chemotherapy; * History of other prior or concurrent malignancies, except those with complete treatment and disease-free survival for more than 5 years; * Presence of an active, known or suspected autoimmune disease, or requirement for long-term systemic corticosteroid therapy (equivalent to ≥ 10 mg prednisone daily) or other immunosuppressive agents. Participants using inhaled or topical corticosteroids will not be excluded; * Presence of ascites, hepatic encephalopathy, sclerosing cholangitis, or other concurrent organ dysfunctions that would preclude tolerance of general anesthesia or hepatectomy; * Women who are breastfeeding or pregnant; * Any other factors that, in the investigator's judgment, may compromise participant safety or trial compliance, including serious comorbidities requiring ongoing treatment, clinically significant laboratory abnormalities, or relevant social or family-related issues.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response (MPR) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Residual viable tumor cell ratio | 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. | Postoperative resected specimens are analyzed via pathological section to determine the residual viable tumor cell ratio |
| Objective Response Rate (ORR) | From enrollment until 2-4 weeks after completion of neoadjuvant therapy (three cycles, each cycle is 21 days) | 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. |
| Pathologic Response Rate (PCR) | 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. | No viable tumor cells are found in the review of pathological sections. |
| R0 resection | 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. | R0 resection rate refers to the proportion of patients achieving complete surgical resection with negative margins. |
| Overall Survival (OS) | From enrollment up to 2 years following treatment initiation | OS is defined as the time from participant receiving the first treatment until death from any cause. |
| Disease-free survival (DFS) | From enrollment up to 2 years following treatment initiation | 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. |
Contacts
CONTACTYifan Tong, Ph.D
PRINCIPAL_INVESTIGATORYuelong Liang, Ph.D
Sir Run Run Shaw Hospital, Schoole of Medicine, Zhejiang University
Outcome results
None listed