Durvalumab with gemcitabine, cisplatin, and nab‑paclitaxel for advanced or metastatic gallbladder cancer

A Phase II Study of Gemcitabine, Cisplatin, Nab-Paclitaxel, and Durvalumab in Locally Advanced or Metastatic Gallbladder Cancer

This trial will test whether adding the immune drug durvalumab to chemotherapy (gemcitabine, cisplatin, and nab‑paclitaxel) helps adults with unresectable locally advanced or metastatic gallbladder cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: durvalumab, prednisone, chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06591650 on ClinicalTrials.gov

What this trial studies

This phase II interventional trial gives adults with unresectable locally advanced or metastatic gallbladder adenocarcinoma a combination of gemcitabine, cisplatin, and nab‑paclitaxel together with the PD‑L1 inhibitor durvalumab. Treatment is delivered in repeated cycles and participants undergo regular imaging using RECIST 1.1 plus laboratory monitoring to follow tumor response and safety. Eligible patients must have ECOG performance status 0–1, measurable disease, no prior systemic therapy for gallbladder cancer, and adequate bone marrow, liver, and renal function. The study measures objective response and toxicity as primary outcomes and tracks progression‑free and overall survival as key secondary outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with histologically confirmed unresectable locally advanced or metastatic gallbladder adenocarcinoma, ECOG 0–1, measurable disease, adequate organ function, and no prior systemic therapy for gallbladder cancer.

Not a fit: Patients with poor performance status (ECOG ≥2), prior systemic therapy for gallbladder cancer, uncontrolled organ dysfunction, or rapidly declining health are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this combination could increase tumor shrinkage and lengthen disease control, potentially improving survival and symptoms for people with advanced gallbladder cancer.

How similar studies have performed: Related approaches combining PD‑L1 inhibitors with gemcitabine and cisplatin have shown positive results in advanced biliary tract cancers (for example TOPAZ‑1), while adding nab‑paclitaxel has produced mixed but encouraging signals in smaller studies.

Eligibility criteria

Inclusion Criteria:

1. Age≥18 years at time of study entry.
2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Has histologically or cytologically confirmed unresectable locally advanced or metastatic gallbladder adenocarcinoma.
4. Has at least 1 measurable disease, as defined by RECIST 1.1, at baseline.
5. Has a life expectancy ≥ 3 months from proposed first dose date.
6. Has received no prior anti-cancer therapy for gallbladder adenocarcinoma.
7. Has adequate bone marrow, liver and renal functions measured within 14 days prior to administration of study treatment: Absolute neutrophil count≥1.5 x109/L;Platelet count≥100×109/L;Serum bilirubin≤2.5×institutional upper limit of normal (ULN). Subjects requiring biliary decompression, biliary stent, or drainage using percutaneous trans-hepatic cholangiogram are allowed (patients with a declining bilirubin status post stent placement are eligible with serum bilirubin≤2.5×ULN);Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)≤2.5×ULN;Measured creatinine clearance (CL)\>50 mL/min or calculated creatinine CL\> 50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
8. Women with childbearing potential should complete a pregnancy test with negative result within 28 days of study treatment and be willing to use effective contraceptive methods from screening to 90 days after the last dose of durvalumab
9. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm from screening to 90 days after the last dose of durvalumab.
10. Capable of giving written informed consent, prior to any study specific procedures,and ability to comply with the study protocol in the investigator\'s judgment.

Exclusion Criteria:

1. Diagnosis of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma or carcinoma of Vaters ampulla.
2. Known hypersensitivity to any of the study drugs or any of the study drug excipients.
3. Patients, who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 therapy.
4. Has an active or previously documented autoimmune or inflammatory disorder (including inflammatory bowel disease \[e.g., colitis or Crohn\'s disease\], diverticulitis \[diverticulosis is not an excluding factor\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves\' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]).
5. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; Patients having any chronic skin condition that does not require systemic therapy; Patients without active disease in the last 5 years (allowed only after consultation with the study physician); Patients with celiac disease controlled by diet alone.
6. Has history of allogenic organ transplantation.
7. Has a history of active primary immunodeficiency.
8. Has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection; symptomatic congestive heart failure; uncontrolled hypertension; unstable angina pectoris; cardiac arrhythmia; interstitial lung disease; serious chronic gastrointestinal conditions associated with diarrhea; or psychiatric illness/social situations that would limit compliance with study requirements, would substantially increase risk of incurring adverse events (AEs), or would compromise the ability of the patient to give written informed consent.
9. Has a prior history of myocardial infarction, transient ischemic attack, or stroke within the past 3 months prior to the scheduled first dose of study treatment.
10. Has a history of another primary malignancy. Patients having the following are still eligible: Malignancy treated with curative intent, no known active disease \>= 5 years before the first dose of IP, and low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated carcinoma in situ without evidence of disease.
11. Has active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), hepatitis B (presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥10 IU/mL), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (hepatitis C virus \[HCV\]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
12. Is currently using or previously used immunosuppressive medication within 14 days before the first dose of durvalumab. The following medications are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication).
13. Is a female and pregnant or breastfeeding; or is a male or female of reproductive potential who is not willing to employ effective birth control from time of screening to 90 days after the last dose of durvalumab.
14. Participated in another clinical study with an investigational product during the last 4 weeks from the first dose of this study\'s treatment.
15. Is concurrently enrolled in another clinical study (patient is eligible if the study is an observational (non interventional) study or if enrollment is during the follow-up period of an interventional study.
16. Is unsuitable to participate in the study or is unlikely to comply with study procedures, restrictions and requirements (per judgment by the investigator).

Where this trial is running

Shanghai, Shanghai Municipality

• Hepatobiliary Surgery Center, Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Lun xiu Qin — Fudan University
• Study coordinator: Xiangyu Wang

Conditions Gallbladder Cancer Unresectable