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

NCT07030140 | Recruiting Phase 2

• 1 other identifier: SDZLEC2024-364-03
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Hilar Cholangiocarcinoma; Bile Duct Cancer; Cholangiocarcinoma

Keywords

Borderline Resectable; Unresectable; SBRT; Tislelizumab; Gemcitabine; Cisplatin; Oxaliplatin; Neoadjuvant Therapy; Immunotherapy; Radiation Therapy; PD-1 Inhibitor; Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Defined as the time from initiation of treatment to death from any cause.

  Up to 36 months

Secondary Outcomes (5)

• R0 Resection Rate

  At the time of surgery (approx. 3-6 months from enrollment)

• Pathological Complete Response (pCR)

  At the time of surgery

• Progression-Free Survival (PFS)

  Up to 24 months

• Local Control Rate

  6, 12, 18, and 24 months

• Treatment-related Adverse Events

  From treatment initiation up to 90 days after last dose

Study Arms (1)

Tislelizumab + SBRT + GP Chemotherapy

EXPERIMENTAL

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.

Radiation: Stereotactic Body Radiotherapy (SBRT); Drug: Tislelizumab; Drug: Gemcitabine; Drug: Cisplatin or Oxaliplatin

Interventions

Stereotactic Body Radiotherapy (SBRT) 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 + SBRT + GP Chemotherapy

Tislelizumab 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.

Tislelizumab + SBRT + GP Chemotherapy

Gemcitabine DRUG

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

Tislelizumab + SBRT + GP Chemotherapy

Cisplatin or Oxaliplatin 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.

Tislelizumab + SBRT + GP Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jinbo Yue: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, 250117, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma; Klatskin Tumor; Bile Duct Neoplasms; Biliary Tract Neoplasms

Interventions

Radiosurgery; tislelizumab; Gemcitabine; Cisplatin; Oxaliplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Jinbo Yue

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

• Bo Zhang

  Shandong Cancer Hospital and Institute

  STUDY CHAIR

Central Study Contacts

Jinbo Yue

CONTACT

053167626442; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Radiation Oncology

Model Details: Single-arm design with sequential SBRT followed by Tislelizumab plus GP chemotherapy

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: June 22, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2025-06

Locations

CN (1)