NCT07030140

Phase II Study of Neoadjuvant Tislelizumab Plus Radiotherapy and GP Chemotherapy for Borderline/Unresectable Hilar Cholangiocarcinoma

A Phase II, Single-arm, Prospective Clinical Study of Neoadjuvant Therapy With Tislelizumab Combined With Radiotherapy and Gemcitabine-Platinum Chemotherapy for Borderline Resectable or Unresectable Hilar Cholangiocarcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Jinbo Yue · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II, single-arm, prospective clinical trial designed to evaluate the efficacy and safety of neoadjuvant therapy combining stereotactic body radiotherapy (SBRT), GP chemotherapy (gemcitabine and cisplatin/oxaliplatin), and tislelizumab in patients with borderline resectable or unresectable hilar cholangiocarcinoma. Eligible patients will receive SBRT followed by three cycles of tislelizumab plus GP chemotherapy. Patients with resectable disease after evaluation may undergo surgery and receive postoperative treatment as recommended by the multidisciplinary team. Those who remain unresectable will receive three additional cycles of systemic therapy. The primary endpoint is overall survival (OS); secondary endpoints include R0 resection rate, pathological complete response (pCR), surgical difficulty, progression-free survival (PFS), local control rate, and treatment-related safety.

Detailed description

Hilar cholangiocarcinoma is a rare but highly aggressive malignancy, often diagnosed at advanced stages due to its asymptomatic progression and challenging anatomical location. R0 resection remains the cornerstone of curative therapy, but many patients are initially considered borderline resectable or unresectable due to vascular involvement or lymph node metastasis. Recent studies suggest that neoadjuvant therapy may improve resectability and survival outcomes by reducing tumor burden and modulating the tumor microenvironment. Stereotactic body radiotherapy (SBRT) offers precise local control, while GP chemotherapy (gemcitabine and cisplatin/oxaliplatin) has demonstrated efficacy in biliary tract cancers. Immunotherapy with PD-1 inhibitors, such as tislelizumab, has shown promise in enhancing antitumor immunity, especially when combined with radiotherapy and chemotherapy. This phase II, single-arm, prospective study aims to evaluate the efficacy and safety of neoadjuvant SBRT followed by tislelizumab and GP chemotherapy in patients with borderline resectable or unresectable hilar cholangiocarcinoma. Patients will first receive SBRT to the gross tumor volume (GTV) at a dose of either 5Gy × 5-8 fractions or 4Gy × 15 fractions. After radiotherapy, participants will receive three cycles of tislelizumab (200mg Q3W) in combination with gemcitabine (1000mg/m² on Days 1 and 8) and cisplatin (25mg/m² on Days 1 and 8) or oxaliplatin (100mg/m² on Day 1), repeated every 21 days. Patients will be re-evaluated after three cycles. If resectable, patients may undergo surgery, followed by additional postoperative therapy based on MDT recommendations. If unresectable, an additional three cycles of systemic therapy will be administered. The primary endpoint is overall survival (OS). Secondary endpoints include R0 resection rate, pathological complete response (pCR), surgical difficulty, local control rate, progression-free survival (PFS), and treatment-related adverse events.

Conditions

• Cholangiocarcinoma
• Hilar Cholangiocarcinoma
• Bile Duct Cancer

Interventions

Type	Name	Description
RADIATION	Stereotactic Body Radiotherapy (SBRT)	SBRT to the primary tumor and metastatic lymph node at a dose of either 5 Gy × 5-8 fractions or 4 Gy × 15 fractions, delivered prior to systemic therapy.
DRUG	Tislelizumab	Tislelizumab 200 mg administered intravenously every 3 weeks (on Day 1 of each 21-day cycle), for three to six cycles depending on surgical eligibility.
DRUG	Gemcitabine	Gemcitabine 1000 mg/m² administered intravenously on Days 1 and 8 of each 21-day cycle, for three to six cycles.
DRUG	Cisplatin or Oxaliplatin	Cisplatin 25 mg/m² on Days 1 and 8 or oxaliplatin 100 mg/m² on Day 1 of each 21-day cycle, selected based on patient condition, for three to six cycles.

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-07-01
• Completion: 2028-01-01
• First posted: 2025-06-22
• Last updated: 2025-06-22