Biliary Tract Cancer
Conditions
Brief summary
This Phase II, single-arm, single-center study evaluates the conversion to resectability and safety of Ivonescimab combined with liposomal irinotecan and 5-FU/LV in patients with potentially resectable biliary tract malignancies. Eligible patients receive three cycles of the combination therapy every 3 weeks, followed by surgery. Post-surgery, patients resume treatment for three more cycles and then continue with evoracizumab alone for up to 1 year. Safety is monitored through AE and SAE assessments for at least 30 and 90 days post-last dose, respectively. Biomarker exploration is also conducted in consenting patients.
Detailed description
This trial is a prospective, single-arm, single-center Phase II study to evaluate the success, safety, and tolerability of surgical conversion of Ivonescimab in combination with irinotecan liposome injection and 5-FU/LV in patients with potentially resectable biliary malignancies. The study included a screening period (no more than 28 days after subjects signed informed consent to the first treatment), a treatment period (including in-treatment visits and end-of-treatment visits), and a follow-up period (including safety visits, disease progression visits, and survival visits). After signing the informed consent, the subjects underwent a screening period within 28 days prior to the initial treatment to determine their eligibility for the study. After the subjects signed the informed consent, the subjects who met the screening criteria were selected to receive Ivonescimab combined with irinotican liposome injection and 5-FU/LV, administered once every 3 weeks, and then given radical surgical treatment at an elective time after 3 cycles. Successful conversion subjects resumed treatment within 8 weeks after surgery and received Ivonescimab combined with irinotecan liposome injection and 5-FU/LV every 3 weeks, and continued to receive Ivonescimab treatment for 1 year after 3 cycles. The safety of the medication is evaluated, and depending on the severity of adverse events (AE) that occur and are associated with the drug, the investigator will take measures to ensure the safety of the subject. After the final dosing, each subject will receive at least 30 days of follow-up AE monitoring and at least 90 days of follow-up SAE monitoring to evaluate subsequent safety. Biomarkers for predictive efficacy will also be explored, biomarker blood and tumor samples will be collected at baseline and during the trial for subjects who have signed up for biomarker sample collection/collection. Administration regimen: 1. Ivonescimab: 20mg/kg, d1, ivgtt, Q3W 2. Irinotecan liposomes: 70mg/m2, d1, ivgtt, Q3W 3. Calcium folinate 400mg/m2, d1, ivgtt, Q3W 4.5-FU 2400mg/m2, d1, ivgtt, Q3W
Interventions
DRUGIvonescimab+chemotherapy
Dosing Schedule: 1. Ivonescimab: 20 mg/kg, Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 2. Irinotecan Liposome: 70 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 3. Calcium Folinate (LV): 400 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 4. 5-FU: 2400 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W).
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients eligible for inclusion in this study must meet all of the following criteria: 1. Informed Consent: Able to provide written informed consent and understand and agree to comply with study requirements and the assessment schedule. 2. Age and Gender: Age ≥18 years and ≤75 years on the day of signing the Informed Consent Form (ICF), male or female. 3. Disease Status: Potentially resectable, previously untreated biliary tract malignancy confirmed by histological or cytological evidence. 4. Tumor Assessment: Tumor evaluated by a hepatobiliary surgeon with sufficient objective evidence to determine irresectability. 5. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6. Life Expectancy: Estimated survival of more than 12 weeks. 7. Body Weight: Weight \>30 kg. 8. Prior Therapy: No prior anti-tumor therapy, including but not limited to anti-CTLA-4, anti-VEGF, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies. 9. EnEnough Organ Function 10. Coagulation: Prothrombin time (PT) ≤1.5×ULN, international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN. 11. Blood Pressure: Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg during the screening period, with or without antihypertensive medication. No changes to antihypertensive therapy within 1 week prior to the first administration of the study drug. 12. Contraception: Sexually active males and females of childbearing potential (not surgically sterilized) must agree to use a medically accepted method of contraception (e.g., intrauterine device, contraceptive pill, or condom) during the study treatment period and for 6 months after the last dose of study treatment. • Females of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-HCG) test within 7 days prior to study enrollment and must not be breastfeeding. 13. HBV Management: Patients with detectable HBV DNA levels (≥10 IU/mL or above the limit of detection) and HBV infection (defined as positive hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[anti-HBc\]) must receive antiviral therapy according to clinical practice prior to study treatment to ensure adequate viral suppression. Antiviral therapy must be continued during the study period and for 6 months after the last dose of study treatment. Patients with positive anti-HBc but undetectable HBV DNA (\<10 IU/mL or below the limit of detection) do not require antiviral therapy unless HBV DNA exceeds 10 IU/mL or the limit of detection during the study. Patients with active HBV and HCV co-infection (defined by positive anti-HCV antibody) or active HBV and hepatitis D virus co-infection are excluded. 14. Voluntary Participation: Willing to voluntarily participate in the clinical trial, comply with study visits and procedures, understand the study requirements, and have signed the informed consent form.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| surgical conversion success rate | From the start of conversion therapy until surgical evaluation or resection, or until it is determined that surgical resection is not feasible. | Surgical conversion success rate refers to the percentage of subjects who achieve relief after treatment and undergo surgical treatment among the evaluable cases, while also calculating the R0 resection rate and the relief situation based on postoperative pathology. |
Countries
China
Contacts
Primary ContactLu chen, MD
Outcome results
None listed