Biliary Tract Cancer (BTC), Surgery, Radiotherapy
Conditions
Keywords
Biliary Tract Cancer (BTC), Lymph Node Metastases, Primary Tumor Resection, Postoperative Radiotherapy
Brief summary
This is a multicenter, open-label, single-arm, prospective phase II clinical study. Eligible patients with lymph node-positive biliary tract cancer will undergo primary tumor resection with selective lymph node dissection. During surgery, the regional and retroperitoneal lymph nodes will be explored, and lymph nodes that are technically amenable to surgical resection will be dissected. Metastatic lymph nodes that cannot be safely or completely resected because of local invasion or because of their location beyond the feasible surgical dissection field will not be surgically resected and will subsequently be treated with postoperative radiotherapy. Following surgery, patients will receive postoperative radiotherapy to the primary tumor bed and involved/regional lymph node areas. For patients who undergo R0 or R1 resection, concurrent chemoradiotherapy with capecitabine or S-1 will be administered for 2 cycles, followed by 6 cycles of adjuvant chemotherapy. For patients who undergo R2 resection, concurrent radiotherapy with capecitabine or S-1, with or without a PD-1/PD-L1 inhibitor, will be administered, followed by maintenance therapy with capecitabine or S-1, with or without a PD-1/PD-L1 inhibitor, until disease progression or unacceptable toxicity.
Interventions
PROCEDUREPrimary Tumor Resection and Selective Lymph Node Dissection
Patients will undergo primary tumor resection with selective lymph node dissection. During surgery, regional and retroperitoneal lymph nodes will be explored, and lymph nodes that are technically amenable to surgical resection will be selectively dissected. Metastatic lymph nodes that cannot be safely or completely resected because of local invasion or because they extend beyond the feasible surgical dissection field will not be surgically resected and will subsequently be treated with postoperative radiotherapy.
RADIATIONPostoperative Radiotherapy
All patients will receive postoperative radiotherapy using intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT). For patients undergoing R0/R1 resection, the high-risk tumor bed, including narrow-margin or lymph node-positive tumor beds, will receive 55-65 Gy in 20-25 fractions, while elective nodal regions will receive 40-45 Gy in 20-25 fractions. Radiotherapy to the primary tumor bed may be omitted when the surgical margin is considered adequate. For patients undergoing R2 resection, the high-risk tumor bed will receive 55-65 Gy in 20-25 fractions, residual metastatic lymph nodes will receive 60-70 Gy in 20-25 fractions, and elective nodal regions will receive 40-45 Gy in 20-25 fractions. Radiotherapy to the primary tumor bed may be omitted when the surgical margin is considered adequate.
For patients undergoing R0/R1 resection, capecitabine or S-1 will be administered concurrently with radiotherapy for 2 cycles, followed by 6 cycles of adjuvant chemotherapy. Capecitabine will be administered at 1,600 mg/m² on Days 1-14 every 21 days during radiotherapy and 2,000 mg/m² on Days 1-14 every 21 days for 6 subsequent cycles. For patients intolerant to capecitabine, S-1 will be substituted: concurrent S-1 40-50 mg twice daily on Days 1-28, every 42 days for 1 cycle, followed by maintenance S-1 40-60 mg twice daily on Days 1-28, every 42 days for 3 cycles. For patients undergoing R2 resection, capecitabine or S-1, with or without a PD-1/PD-L1 inhibitor, will be administered concurrently with radiotherapy, followed by maintenance treatment with the same regimen until disease progression or unacceptable toxicity.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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. Patients with suspected biliary tract carcinoma who are eligible for surgical exploration, with postoperative pathological confirmation of biliary tract adenocarcinoma; 2. Age 18-80 years; 3. Preoperative assessment indicating that the primary tumor is potentially amenable to R0/R1 resection; 4. Preoperative evidence of lymph node metastases with at least one of the following features indicating that complete surgical resection or lymph node dissection may not be feasible: * Local invasion of regional lymph nodes, such that complete surgical resection may not be feasible; * Retroperitoneal lymph node metastases extending beyond the feasible surgical dissection field; 5. Whole-body PET/CT demonstrating metastatic lymph node involvement confined to a contiguous extended lymphatic field that can be encompassed within a single radiotherapy plan, with the involved lymph nodes extending from the lower paraesophageal lymph node region superiorly to the lymph nodes at the level of the abdominal aortic bifurcation inferiorly; 6. No distant organ metastases, non-regional lymph node metastases, or intrahepatic metastatic lesions are allowed. Isolated right internal mammary lymph node or left supraclavicular lymph node involvement is permitted; however, these lesions will not be included in the initial radiotherapy field and may receive subsequent definitive local radiotherapy based on multidisciplinary evaluation and treatment response; 7. Prior systemic therapy, including chemotherapy, targeted therapy, or immunotherapy, is permitted. Prior local treatment, including interventional therapy or radiofrequency ablation, is not permitted; 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and a life expectancy of \>3 months; 9. Child-Pugh class A5 or A6; 10. Liver function meeting the following criteria: * ALT ≤2.5 × the upper limit of normal (ULN), with AST ≤6 × ULN when ALT ≤1.5 × ULN and AST ≤2.5 × ULN when ALT \>1.5 × ULN but ≤2.5 × ULN, after excluding AST elevation due to myocardial infarction; * Total bilirubin (TBIL) \<60 μmol/L. 11. No clinically significant abnormalities on electrocardiography, no significant cardiac insufficiency, and no contraindication to treatment with PD-1/PD-L1 inhibitors; 12. Adequate renal function, defined as serum creatinine (CRE) and blood urea nitrogen (BUN) ≤2.5 × ULN; 13. Adequate hematologic function, defined as hemoglobin (Hb) ≥80 g/L, absolute neutrophil count (ANC) ≥0.5 × 10⁹/L, and platelet count (PLT) ≥80 × 10⁹/L; 14. Patients voluntarily participate in this clinical trial and sign an informed consent form.
Exclusion criteria
1. Current participation in another interventional clinical trial involving an investigational drug or treatment; 2. Previous abdominal radiotherapy or liver transplantation; 3. Previous local treatment for the current malignancy, including interventional therapy or radiofrequency ablation; 4. Known or suspected drug dependence, substance abuse, or alcohol abuse; 5. Pregnancy or breastfeeding; 6. Severe psychiatric or neurological disorders that may interfere with the ability to provide informed consent or with the reporting or assessment of adverse events; 7. Concurrent second primary malignancy or a history of another malignancy diagnosed within 3 years before enrollment, except for superficial skin cancers, localized low-grade malignancies, or carcinoma in situ that have been adequately treated and are not considered potentially life-threatening due to disease progression; 8. Severe unhealed wounds, ulcers, or fractures; 9. Biliary fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks before enrollment; 10. Unstable angina, myocardial infarction, coronary artery bypass grafting, congestive heart failure, or cerebrovascular events, including transient ischemic attack or pulmonary embolism, within 3 months before enrollment; 11. Persistent arrhythmia of CTCAE grade ≥2, atrial fibrillation of any grade, or prolonged QTc interval (QTc \>450 ms in males or \>470 ms in females); 12. Known HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | 24 months | Median Overall Survival (mOS) is defined as the median of Overall Survival (OS). OS is defined as the time from the date of surgery to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival | 24 months | Median Progression-free Survival (mPFS) is defined as the median of Progression-free Survival (PFS). PFS is defined as the time from the date of surgery until tumor progression or death from any cause. |
| R0/R1 resection rate | At the completion of surgery | R0/R1 Resection Rate is defined as the percentage of patients who achieve R0 or R1 resection among all patients undergoing surgery |
| Completion Rate of Treatment Protocol | Up to 6 months after surgery | Completion Rate of the Surgery Plus Radiotherapy Treatment Protocol is defined as the percentage of patients who complete both planned surgery and postoperative radiotherapy according to the study protocol. |
| Objective Response Rate (ORR) in Patients Undergoing R2 Resection | Assessment in 1 to 3 months after radiotherapy | Objective Response Rate (ORR) After Postoperative Radiotherapy in Patients Undergoing R2 Resection is defined as the percentage of patients with R2 resection who achieve complete response (CR) or partial response (PR) as their best overall response within 3 months after completion of postoperative radiotherapy, according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST 1.1. |
| Incidence of Grade ≥3 Adverse Events Following Postoperative Radiotherapy | 24 months | Adverse events are assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The outcome is defined as the proportion of patients who experience grade ≥3 adverse events following postoperative radiotherapy. |
Countries
China
Contacts
CONTACTBo Chen, MD
Outcome results
None listed