Sintilimab Plus NALIRIFOX or Gemcitabine-Cisplatin as First-Line Treatment for Metastatic Biliary Tract Cancer

NCT07831993 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-0960-03
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, noncomparative, open-label, exploratory clinical study designed to evaluate the efficacy and safety of sintilimab in combination with NALIRIFOX or gemcitabine plus cisplatin (GP) as first-line treatment for patients with metastatic biliary tract cancer (BTC) who have not received prior systemic anticancer therapy for metastatic disease. Approximately 54 eligible participants will be randomized in a 1:1 ratio to two treatment groups. Participants in Group A will receive sintilimab in combination with NALIRIFOX, consisting of liposomal irinotecan (II), 5-fluorouracil/leucovorin, and oxaliplatin. Participants in Group B will receive sintilimab in combination with gemcitabine and cisplatin. 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), and safety.

Conditions

Biliary Tract Cancer

Keywords

Biliary Tract Cancer; Sintilimab; NALIRIFOX; Liposomal Irinotecan

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of participants who achieve 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.

  Every 6 weeks (±7 days) from the first dose of study treatment until disease progression, up to 25 months.

Secondary Outcomes (9)

• Disease Control Rate (DCR)

  Every 6 weeks (±7 days) from the first dose of study treatment until disease progression, up to 25 months.

• Progression-Free Survival (PFS)

  From enrollment and initiation of study treatment until the first documented radiographic disease progression or death from any cause, whichever occurs first, assessed up to 25 months.

• Overall Survival (OS)

  From enrollment and initiation of study treatment until death from any cause, assessed up to 25 months.

• Number and Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

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

• Number and Percentage of Participants With Serious Adverse Events (SAEs)

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

Study Arms (2)

Sintilimab Plus NALIRIFOX

EXPERIMENTAL

Participants will receive sintilimab in combination with NALIRIFOX, consisting of liposomal irinotecan (II), 5-fluorouracil/leucovorin, and oxaliplatin. Participants without disease progression after 12 cycles of combination therapy will receive maintenance treatment with liposomal irinotecan (II), 5-fluorouracil/leucovorin, and sintilimab.

Drug: Sintilimab; Drug: Irinotecan Hydrochloride Liposome Injection (II); Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Sintilimab Plus Gemcitabine and Cisplatin

EXPERIMENTAL

Participants will receive sintilimab in combination with gemcitabine and cisplatin (GP). Participants without disease progression after 8 cycles of combination therapy will receive maintenance treatment with gemcitabine and sintilimab.

Drug: Sintilimab; Drug: gemcitabine; Drug: Cisplatin

Interventions

Sintilimab DRUG

Sintilimab 200 mg is administered by intravenous infusion on Day 1 every 3 weeks (Q3W) during combination treatment. Sintilimab is continued during maintenance treatment in participants without disease progression, according to the assigned treatment arm.

Sintilimab Plus Gemcitabine and Cisplatin; Sintilimab Plus NALIRIFOX

Irinotecan Hydrochloride Liposome Injection (II) DRUG

Irinotecan hydrochloride liposome injection (II) 50 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). It is administered as part of the NALIRIFOX regimen and is continued during maintenance treatment in eligible participants without disease progression.

Sintilimab Plus NALIRIFOX

Oxaliplatin DRUG

Oxaliplatin 60 mg/m² is administered by intravenous infusion over 2 hours, or according to institutional clinical practice, on Day 1 every 2 weeks (Q2W) as part of the NALIRIFOX combination treatment. Oxaliplatin is not included in the maintenance regimen.

Sintilimab Plus NALIRIFOX

Leucovorin DRUG

Leucovorin 200 mg/m² is administered by intravenous infusion over 1 hour, or according to institutional clinical practice, on Day 1 every 2 weeks (Q2W) as part of the NALIRIFOX regimen. Leucovorin is continued during maintenance treatment in eligible participants without disease progression.

Sintilimab Plus NALIRIFOX

Fluorouracil DRUG

Fluorouracil 2000 mg/m² is administered as a continuous intravenous infusion over 46 to 48 hours, or according to institutional clinical practice, starting on Day 1 every 2 weeks (Q2W) as part of the NALIRIFOX regimen. Fluorouracil is continued during maintenance treatment in eligible participants without disease progression.

Sintilimab Plus NALIRIFOX

gemcitabine DRUG

Gemcitabine 1000 mg/m² is administered by intravenous infusion over 30 minutes on Days 1 and 8 of each 3-week cycle (Q3W). It is administered with cisplatin and sintilimab during combination treatment and is continued with sintilimab during maintenance treatment in eligible participants without disease progression.

Sintilimab Plus Gemcitabine and Cisplatin

Cisplatin DRUG

Cisplatin 25 mg/m² is administered by intravenous infusion on Days 1 and 8 of each 3-week cycle (Q3W) as part of the gemcitabine, cisplatin, and sintilimab combination regimen. Cisplatin is not included in the maintenance regimen.

Sintilimab Plus Gemcitabine and Cisplatin

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 75 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.
• Presence of distant metastasis at the current disease stage.
• 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);
• 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);

You may not qualify if:

• Tumor- and treatment-related criteria:
• History of a malignancy other than biliary tract cancer within 5 years before screening, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancies considered by the investigator 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.
• Medical history or concomitant diseases:
• Severe gastrointestinal dysfunction documented clinically, including bleeding or obstruction, inflammation of NCI-CTCAE version 5.0 grade \>2, diarrhea of NCI-CTCAE version 5.0 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 5.0 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;

Sponsors & Collaborators

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

Study Sites (1)

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

sintilimab; Oxaliplatin; Leucovorin; Fluorouracil; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Juan Du, MD

  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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a 1:1 ratio to receive either sintilimab plus NALIRIFOX or sintilimab plus gemcitabine and cisplatin (GP).

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 21, 2026
• Study Start: January 14, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 21, 2026

Record last verified: 2026-01

Locations

CN (1)