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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Overall Survival (OS) [Time frame: Up to 36 months]

Secondary outcome measures (5)

• R0 Resection Rate [Time frame: At the time of surgery (approx. 3-6 months from enrollment)]
• Pathological Complete Response (pCR) [Time frame: At the time of surgery]
• Progression-Free Survival (PFS) [Time frame: Up to 24 months]
• Local Control Rate [Time frame: 6, 12, 18, and 24 months]
• Treatment-related Adverse Events [Time frame: From treatment initiation up to 90 days after last dose]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shandong Cancer Hospital and Institute — Jinan

Identifiers

NCT: NCT07030140 · SDZLEC2024-364-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗