PULSAR with dual immunotherapy and chemotherapy for cholangiocarcinoma

Phase I/II Clinical Study of Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) Combined With Immunotherapy and Chemotherapy in Patients With Cholangiocarcinoma

This trial will test whether adding PULSAR radiotherapy to two immunotherapy drugs plus gemcitabine and cisplatin helps people with locally advanced or metastatic cholangiocarcinoma.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: West China Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, radiation
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07291947 on ClinicalTrials.gov

What this trial studies

This phase 1/2 protocol combines PULSAR patterned radiotherapy with dual immune checkpoint blockade (iparomlimab and tuvonralimab [QL1706]) and standard gemcitabine/cisplatin (GC) chemotherapy in patients with locally advanced or metastatic cholangiocarcinoma. After confirming eligibility, patients undergo CT simulation and radiotherapy planning and then receive scheduled cycles of PULSAR radiation together with the two monoclonal antibodies and GC chemotherapy, with response measured by RECIST 1.1. The primary focus is on safety and anti-tumor efficacy, while secondary analyses will examine changes in the tumor microenvironment and systemic immune responses. Routine labs and imaging guide treatment delivery and monitoring of adverse events.

Who should consider this trial

Good fit: Adults 18–75 with histologically or cytologically confirmed locally advanced or metastatic cholangiocarcinoma, at least one measurable lesion, ECOG 0–1, adequate organ function, expected survival ≥3 months, and no contraindications to radiotherapy, PD‑1/CTLA‑4 inhibitors, gemcitabine, or cisplatin.

Not a fit: Patients with ECOG performance status >1, significant organ dysfunction, contraindications to immunotherapy/chemotherapy/radiotherapy, or an expected survival under three months are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve tumor control and survival while stimulating stronger anti-tumor immune responses.

How similar studies have performed: Combining radiation with immune checkpoint inhibitors and chemotherapy has shown promising signals in other cancers, but the specific PULSAR plus dual‑checkpoint and GC chemotherapy approach in cholangiocarcinoma is largely experimental with limited published evidence.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent. The subject has fully understood and accepted the purpose, content, expected efficacy, mechanism of action, and risks of the study, and has signed the informed consent form.
2. Age 18-75 years, regardless of gender.
3. Histopathologically or cytologically confirmed locally advanced or metastatic cholangiocarcinoma.
4. At least one measurable lesion based on RECIST 1.1 criteria.
5. ECOG performance status score of 0-1.
6. Expected survival time ≥3 months.
7. Willing to comply with study procedures and able to undergo treatment (including radiotherapy, immunotherapy, chemotherapy) and follow-up.
8. No contraindications to the use of PD-1, PD-L1 inhibitors, gemcitabine, or cisplatin.
9. No contraindications to radiotherapy.
10. Organ function levels meet the following requirements: - Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; - Platelet (PLT) count ≥ 80 × 10⁹/L; - Hemoglobin (Hb) level ≥ 90 g/L; - Total bilirubin (TBil) level ≤ 1.5 times the upper limit of normal (ULN); - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN; if liver metastases are present, ≤ 5 times ULN; - Serum creatinine ≤ 1.5 times ULN, or calculated creatinine clearance rate ≥ 50 ml/min; - International normalized ratio (INR) ≤ 1.5 times ULN, and prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN, unless the subject is receiving anticoagulant therapy. - Hepatitis B surface antigen (HBsAg) positive with peripheral blood hepatitis B virus DNA (HBV-DNA) titer ≤ 1 × 10³ copies/L; if HBsAg positive and peripheral blood HBV-DNA titer ≥ 1 × 10³ copies/L, subjects may be included if the investigator determines that the chronic hepatitis B is stable and poses no additional risk.
11. Women of childbearing potential must agree to use appropriate contraceptive measures during the study period. Additionally, a serum or urine pregnancy test performed within 24 hours prior to the initiation of chemotherapy must be negative.
12. Women must be non-lactating.

Exclusion Criteria:

1. Previously treated with anti-PD-1 or anti-PD-L1 antibodies.
2. Received any investigational drug treatment within 4 weeks prior to the first administration of the study drug.
3. Simultaneous participation in other clinical studies, unless it is an observational (non-interventional) clinical study or the follow-up phase of an interventional clinical study.
4. Previously received radiotherapy to the upper abdomen.
5. Uncontrolled severe diseases that the investigator considers may affect the subject's ability to receive study protocol treatment, such as severe cardiac disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled infections, active peptic ulcers, etc.
6. Active known or suspected autoimmune diseases (including but not limited to uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilator treatment). Patients with hypothyroidism requiring hormone replacement therapy and those with skin conditions not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia) may be included.
7. Active tuberculosis infection. Patients with active pulmonary tuberculosis infection within the past year will be excluded, even if treated. Patients with a history of active pulmonary tuberculosis infection more than one year ago will also be excluded unless evidence is provided that they have undergone standard anti-tuberculosis treatment.
8. Patients requiring long-term systemic corticosteroid therapy (equivalent to \>10 mg prednisone/day) or any other form of immunosuppressive therapy. Patients using inhaled or topical corticosteroids may be included.
9. Uncontrolled cardiac disease, such as: New York Heart Association (NYHA) Class II or higher heart failure; unstable angina; myocardial infarction within the past year; clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention. Additionally, dementia, altered mental status, or any psychiatric disorders that could impair the ability to understand, provide informed consent, or complete questionnaires.
10. History of allergy or hypersensitivity to any component of the treatment.
11. History of malignant tumors within the past 5 years, except for completely treated basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, or ductal carcinoma in situ of the breast after radical surgery.
12. Previously received systemic therapy for cholangiocarcinoma.
13. Positive for hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies.
14. Active infection requiring systemic treatment.
15. Other conditions deemed unsuitable for inclusion by the investigator.

Where this trial is running

Chengdu, Sichuan

• West China Hospital — Chengdu, Sichuan, China (RECRUITING)

Study contacts

• Study coordinator: Dr. shu

Conditions: Cholangiocarcinoma, locally advanced or metastatic cholangiocarcinoma, PULSAR, immunotherapy, chemotherapy