Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT for Locally Advanced Biliary Tract Cancer

NCT07797816 | Recruiting Phase 2

• 1 other identifier: 2026-0519-02
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, exploratory interventional study designed to evaluate the efficacy and safety of liposomal irinotecan (II) plus fluorouracil/leucovorin (5-FU/LV) and sintilimab with sequential stereotactic body radiation therapy (SBRT) as first-line treatment for patients with unresectable locally advanced biliary tract cancer (BTC) who have not received prior systemic anticancer therapy for their current disease. Approximately 31 participants will be enrolled. Participants will receive liposomal irinotecan (II), 5-FU/LV, and sintilimab. Participants without disease progression after initial systemic treatment will receive sequential SBRT to the primary biliary tract tumor. After eight administrations of chemotherapy (approximately 16 weeks), resectability will be assessed by a multidisciplinary team. Participants considered eligible for surgery will undergo radical surgical resection followed by adjuvant treatment, whereas those who remain unresectable will continue the study treatment until disease progression or another protocol-defined reason for discontinuation. The primary endpoint is objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), surgical conversion rate (SCR), and safety.

Conditions

Biliary Tract Cancer

Keywords

Locally Advanced Biliary Tract Cancer; Liposomal Irinotecan; Sintilimab; Stereotactic Body Radiation Therapy; Conversion Therapy; First-Line Treatment

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR), as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  From the first dose of study treatment until radiographic disease progression, initiation of new anticancer therapy, death, or study completion, assessed up to approximately 30 months

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  From the first dose of study treatment until radiographic disease progression, initiation of new anticancer therapy, death, or study completion, assessed up to approximately 30 months

• Progression-Free Survival (PFS)

  From enrollment and initiation of study treatment until radiographic disease progression or death from any cause, whichever occurs first, assessed up to approximately 30 months

• Overall Survival (OS)

  From enrollment and initiation of study treatment until death from any cause, assessed up to approximately 30 months

• Surgical Conversion Rate (SCR)

  From initiation of study treatment through multidisciplinary resectability assessment and conversion surgery, if applicable, assessed up to approximately 30 months

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events

  From initiation of study treatment through 30 days (±7 days) after the last dose of study treatment

Study Arms (1)

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

EXPERIMENTAL

Participants will receive liposomal irinotecan (II) plus fluorouracil/leucovorin (5-FU/LV) and sintilimab. Participants without disease progression after four administrations of chemotherapy will receive sequential stereotactic body radiation therapy (SBRT) to the primary biliary tract tumor between the sixth and seventh chemotherapy administrations. After eight administrations of chemotherapy (approximately 16 weeks), participants will undergo multidisciplinary evaluation for surgical resectability. Participants considered eligible for surgery will undergo radical surgical resection followed by four administrations of adjuvant chemotherapy. Participants who remain unresectable will continue the original treatment regimen until disease progression or another protocol-specified reason for discontinuation.

Drug: Irinotecan Hydrochloride Liposome Injection (II); Drug: Fluorouracil; Drug: Leucovorin; Drug: Sintilimab; Radiation: Stereotactic Body Radiation Therapy; Procedure: Radical Surgical Resection

Interventions

Irinotecan Hydrochloride Liposome Injection (II) DRUG

Liposomal irinotecan (II) 60 mg/m² is administered by intravenous infusion over 90 minutes (±30 minutes), or according to institutional clinical practice, on Day 1 every 2 weeks (Q2W).

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

Fluorouracil DRUG

Fluorouracil (5-FU) 2000 mg/m² is administered as a continuous intravenous infusion over 46 hours on Day 1 every 2 weeks (Q2W).

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

Leucovorin DRUG

Leucovorin (LV) 200 mg/m² is administered by intravenous infusion over more than 30 minutes on Day 1 every 2 weeks (Q2W).

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

Sintilimab DRUG

Sintilimab 200 mg is administered by intravenous infusion on Day 1 every 3 weeks (Q3W).

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

Stereotactic Body Radiation Therapy RADIATION

Participants without disease progression after four administrations of chemotherapy will receive stereotactic body radiation therapy (SBRT) to the primary biliary tract tumor between the sixth and seventh chemotherapy administrations. The prescribed radiation doses are 50 Gy in 10 fractions to the planning gross tumor volume (PGTV) and 30 Gy in 10 fractions to the planning target volume (PTV).

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

Radical Surgical Resection PROCEDURE

After eight administrations of chemotherapy (approximately 16 weeks), participants will undergo multidisciplinary evaluation for surgical resectability. Participants considered surgically resectable will undergo radical surgical resection. Successful conversion is defined as R0 or R1 resection.

Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 80 years, inclusive, at the time of signing the informed consent form, regardless of sex.
• Histologically and/or cytologically confirmed biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
• Unresectable locally advanced disease at the current disease stage, as determined by a multidisciplinary team (MDT).
• No prior anticancer treatment for biliary tract cancer at the current disease stage, including radiotherapy, chemotherapy, immunotherapy, or biologic therapy.
• At least one measurable lesion according to RECIST version 1.1. The measurable lesion must not have received prior radiotherapy or other local treatment.
• Expected survival of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, hepatic, renal, cardiac, and coagulation function within 14 days before initiation of study treatment, meeting all of the following requirements:
• Hematologic function: absolute neutrophil count (ANC) ≥1.5 × 10\^9/L; platelet count ≥100 × 10\^9/L; hemoglobin ≥90 g/L (9.0 g/dL); and no blood transfusion or hematopoietic growth factor support for correction within 14 days before screening.
• Biochemical function: serum albumin ≥30 g/L (3.0 g/dL); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × the upper limit of normal (ULN); total bilirubin ≤1.5 × ULN; and serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min as calculated using the Cockcroft-Gault formula.
• Cardiac function: normal 12-lead electrocardiogram or abnormalities considered clinically insignificant by the investigator, with QTcF \<470 ms; and left ventricular ejection fraction (LVEF) ≥50%.
• Coagulation function: prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN and international normalized ratio (INR) ≤1.5 × ULN in participants not receiving anticoagulant therapy. Participants receiving a stable dose of anticoagulant therapy, such as low-molecular-weight heparin or warfarin, may be eligible if the INR is within the expected therapeutic range.
• Willing to participate voluntarily, provide written informed consent, and comply with scheduled study visits and other protocol requirements.

You may not qualify if:

• History of a malignancy other than biliary tract cancer within 5 years before screening, except for cured basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancies considered by the investigator and multidisciplinary team to have a low risk of metastasis and death.
• Known central nervous system (CNS) metastases. Participants with suspected CNS metastases must undergo contrast-enhanced CT or MRI within 28 days before initiation of study treatment to exclude CNS metastases.
• Prior treatment with an immune checkpoint inhibitor, including anti-PD-1, anti-PD-L1, anti-CTLA-4 therapy, or any cellular immunotherapy.
• Prior irinotecan- or liposomal irinotecan-based chemotherapy.
• Use of strong inhibitors or inducers of CYP3A4, CYP2C8, or UGT1A1 within 14 days before initiation of study treatment.
• Participation in another interventional drug clinical trial within 4 weeks before initiation of study treatment, except for observational (non-interventional) studies or follow-up of an interventional clinical study.
• Severe gastrointestinal dysfunction documented clinically, including bleeding or obstruction, inflammation of NCI-CTCAE version 6.0 grade \>2, diarrhea of NCI-CTCAE version 6.0 grade \>1, or other conditions considered by the investigator to potentially affect drug intake, transit, or absorption, including inability to swallow, prior small-bowel resection, or total gastrectomy.
• Pleural effusion or ascites requiring clinical intervention (NCI-CTCAE version 6.0 grade ≥2).
• Serious concomitant conditions that may interfere with study treatment, including any of the following:
• Uncontrolled serious medical disease considered by the investigator to impair the participant's ability to receive protocol-specified treatment, including severe cardiac disease, cerebrovascular disease, uncontrolled diabetes mellitus, uncontrolled hypertension, or active peptic ulcer disease.
• Arterial or venous thrombotic events within 1 year before screening, including cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism, except for catheter-related venous thrombosis from prior chemotherapy that has resolved according to the investigator.
• Tumor involvement of major blood vessels on imaging, or a very high risk, in the investigator's judgment, of tumor invasion into major blood vessels during treatment resulting in potentially fatal hemorrhage.
• History of interstitial lung disease, or noninfectious pneumonitis requiring oral or intravenous corticosteroid therapy.
• Poorly controlled cardiac symptoms or disease, including heart failure greater than New York Heart Association (NYHA) class II, unstable angina, myocardial infarction within 6 months, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
• Positive hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Fluorouracil; Leucovorin; sintilimab; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Juan Du

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan Du, MD

CONTACT

13851668102; dujuanglyy@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will receive liposomal irinotecan (II) plus fluorouracil/leucovorin (5-FU/LV) and sintilimab, with sequential stereotactic body radiation therapy (SBRT). Participants will subsequently undergo multidisciplinary evaluation for potential surgical conversion.

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 1, 2026
• Study Start: January 8, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 1, 2026

Record last verified: 2026-01

Locations

CN (1)