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

NCT ID: NCT07030140

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2028-01-01

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tislelizumab + SBRT + GP Chemotherapy

Participants will receive neoadjuvant stereotactic body radiotherapy (SBRT) followed by three cycles of combination therapy with tislelizumab and GP chemotherapy.

SBRT: 5 Gy × 5-8 fractions or 4 Gy × 15 fractions to the primary tumor. Tislelizumab: 200 mg intravenously every 3 weeks (Day 1 of each cycle). Gemcitabine: 1000 mg/m² IV on Days 1 and 8 of each 21-day cycle. Cisplatin: 25 mg/m² IV on Days 1 and 8 OR Oxaliplatin: 100 mg/m² IV on Day 1 (based on clinical condition). After three cycles, patients will undergo re-evaluation. Those deemed resectable will undergo surgery and receive postoperative therapy based on multidisciplinary assessment. Patients remaining unresectable will receive an additional three cycles of the same systemic therapy.

Group Type: EXPERIMENTAL

Stereotactic Body Radiotherapy (SBRT)

Intervention Type: RADIATION

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.

Tislelizumab

Intervention Type: DRUG

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.

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m² administered intravenously on Days 1 and 8 of each 21-day cycle, for three to six cycles.

Cisplatin or Oxaliplatin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m² administered intravenously on Days 1 and 8 of each 21-day cycle, for three to six cycles.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18-75 years, histologically or cytologically confirmed hilar cholangiocarcinoma
• Borderline resectable or unresectable disease based on imaging and MDT evaluation
• ECOG performance status 0-1
• Adequate hematologic, hepatic, and renal function
• No prior anti-tumor therapy for current diagnosis
• Expected survival ≥ 3 months
• Signed informed consent

Exclusion Criteria

• Evidence of distant metastasis
• Prior treatment with immune checkpoint inhibitors
• Uncontrolled infection or serious medical comorbidities
• Active autoimmune disease requiring systemic therapy
• History of organ transplantation or immunodeficiency
• Pregnancy or lactation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinbo Yue

OTHER

Sponsor Role: lead

Responsible Party

Jinbo Yue

Chief Physician, Radiation Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jinbo Yue

Role: PRINCIPAL_INVESTIGATOR

Shandong Cancer Hospital and Institute

Bo Zhang

Role: STUDY_CHAIR

Shandong Cancer Hospital and Institute

Central Contacts

Jinbo Yue

Role: CONTACT

jbyue@sdfmu.edu.cn

053167626442

Other Identifiers

SDZLEC2024-364-03

Identifier Type: -

Identifier Source: org_study_id