Gallbladder Cancer Unresectable
Conditions
Keywords
gallbladder cancer
Brief summary
This is a single-arm, multicenter, Phase II clinical trial evaluating the efficacy and safety of Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorilimab (a dual anti-PD-1/CTLA-4 bispecific antibody) in patients with advanced unresectable gallbladder cancer. The study aims to assess the surgical conversion rate and objective response rate (ORR) as primary endpoints. Secondary endpoints include R0 resection rate, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profiles. A total of 44 participants will be enrolled across three centers in China. The study is scheduled to run from May 2025 to April 2027.
Interventions
DRUGTreatment :Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorili
Treatment :Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorili
Sponsors
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorilimab (a dual anti-PD-1/CTLA-4 bispecific antibody)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent. * Age 18-75 years. * ECOG performance status 0-2, Child-Pugh class A. * Histologically or cytologically confirmed advanced gallbladder cancer, deemed unresectable for R0 resection. * Adequate organ function: * ANC ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥90 g/L. * Serum creatinine ≤1.2 mg/dL or creatinine clearance ≥60 mL/min. * Total bilirubin ≤1.5×ULN (≤3×ULN if liver metastases); AST/ALT ≤3×ULN (≤5×ULN if liver metastases). * Life expectancy ≥3 months. * Non-pregnant, non-lactating women and willingness to use contraception during and for 3 months after treatment.
Exclusion criteria
* Severe systemic infection or uncontrolled comorbidities (e.g., heart failure, thyroid disease, psychiatric disorders); active autoimmune disease requiring medication. * Known allergy or intolerance to chemotherapy agents. * Prior antitumor therapy (chemotherapy, radiotherapy, immunotherapy) within the past year, or history of other malignancies (except cured cervical carcinoma in situ or non-melanoma skin cancer). * Pregnancy, lactation, or unwillingness to use contraception. * Participation in another clinical trial within 30 days before the first dose. * Unwillingness to participate or inability to provide informed consent. * Any other condition that, in the investigator's judgment, may affect patient safety or compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | At the end of Cycle 6 (each cycle is 21 days) | The objective response rate (ORR) of this quadruplet regimen as first-line therapy |
| Surgical Conversion Rate | At the end of Cycle 6 (each cycle is 21 days) | Proportion of patients who achieve successful conversion to radical resection (R0/R1) after systemic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 Resection Rate | At the end of Cycle 6 (each cycle is 21 days) | Proportion of patients who undergo R0 resection among those who receive surgery. |
| Disease Control Rate (DCR) | At the end of Cycle 6 (each cycle is 21 days) | Proportion of patients with CR, PR, or stable disease (SD) lasting ≥4 weeks. |
| Recurrence-Free Survival (RFS) | up to 2 years | Proportion of patients without recurrence at 2 years after resection. |
| Downstaging Rate | At the end of Cycle 6 (each cycle is 21 days) | Proportion of patients whose clinical stage is reduced after conversion therapy. |
| Adverse Events (AEs) / Serious AEs (SAEs) | through study completion, up to 30 days | Incidence and severity of AEs and SAEs graded by CTCAE v5.0. |
| Surgical Safety | Perioperative | Incidence of surgery-related complications (e.g., infection, bleeding, organ dysfunction) |
| Overall Survival (OS) | through study completion,up to 3 years | Time from enrollment to death from any cause. |
| Pathologic Response Rate | At the end of Cycle 6 (each cycle is 21 days) | Proportion of patients with pathologic downstaging or major pathologic response in resected specimens |
Countries
China
Outcome results
None listed