Combining adebrelimab with apatinib, gemcitabine, and cisplatin for treating biliary tract cancers

A Single-arm Prospective Clinical Study of Adebrelimab in Combination With Apatinib Gemcitabine and Cisplatin for the Neoadjuvant Treatment of Biliary Tract Malignancies

This study is testing a new combination of medications to see if it can help people with high-risk biliary tract cancers do better before surgery.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Fujian Medical University (other)
• Drugs / interventions: chemotherapy, radiation, prednisone, adebrelimab, apatinib
• Locations: 1 site (Fuzhou, Fujian)
• Trial ID: NCT06181032 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a combination treatment involving adebrelimab, apatinib, gemcitabine, and cisplatin for patients with biliary tract malignancies. It is a single-arm, prospective study focusing on neoadjuvant therapy for patients diagnosed with resectable high-risk biliary cancers. The study aims to determine if this regimen can provide longer-term benefits compared to existing treatments. The approach leverages the potential of immunotherapy combined with anti-angiogenic agents to improve outcomes in solid tumors.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with surgically resectable gallbladder cancer or cholangiocarcinoma.

Not a fit: Patients with distant extrahepatic disease or those who have received previous systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the outcomes for patients with biliary tract malignancies by enhancing the effectiveness of neoadjuvant therapy.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy and chemotherapy combinations in advanced biliary malignancies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 1\. Age: 18 years old ≤ 75 years old, both male and female.
* 2\. Patients with gallbladder cancer or cholangiocarcinoma (intrahepatic or extrahepatic) diagnosed by histologic or cytologic examination.
* 3\. high-quality cross-sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) with a diagnosis of surgically resectable high-risk biliary malignancy limited to the liver, bile ducts, and/or regional lymph nodes. (Must meet at least one of the following criteria)
* (1) T-grade ≥ Ib (Ib-IV);
* (2) Single lesion \> 5 cm;
* (3) Multifocal tumors or satellite lesions confined to the same hepatic lobe as the primary lesion but still technically resectable;
* (4) Presence of major vascular invasion but still technically resectable;
* (5) Suspected or involved regional lymph nodes (N1);
* (6) No distant extrahepatic disease (M0).
* 4\. Patients who have not received previous systemic therapy and who, in the judgment of the physician, have no contraindications to surgery, and the patient agrees to undergo radical surgical treatment.
* 5\. At least one measurable lesion (according to the RECIST 1.1 criteria requires that the measurable lesion be ≥10 mm in long diameter on spiral CT scan or ≥15 mm in short diameter in malignant lymph nodes).
* 6\. ECOG PS score of 0-1.
* 7\. Expected survival ≥ 12 weeks.
* 8\. Normal function of major organs and fulfillment of the following criteria:
* (1) Criteria for routine blood tests need to be met: (no blood transfusion within 14 days)
* a. Hemoglobin (HB) ≥ 90g/L;
* b. White blood cell count (WBC) ≥3×109/L;
* c. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
* d. Platelet (PLT) ≥80×109/L.
* (2) Biochemical tests need to meet the following criteria:
* a. Bilirubin (BIL) \<1.5 times the upper limit of normal (ULN);
* b. Glutamine aminotransferase (ALT) and glutamine aminotransferase AST \<5 ULN;
* c. serum creatinine (Cr) ≤ 1.5 ULN.
* 9\. Women of childbearing potential must have a negative pregnancy test (serum) or urine HCG test within 7 days prior to enrollment and be willing to use an appropriate method of contraception for the duration of the trial and for 8 weeks after the last administration of the test drug; in the case of males, they should be surgically sterilized or agree to use an appropriate method of contraception for the duration of the trial and for 8 weeks after the last administration of the test drug.
* 10\. Subjects voluntarily enroll in the study, have good compliance, and cooperate with follow-up visits.

Exclusion Criteria:

* 1\. Pregnant or lactating women.
* 2\. Patients with autoimmune diseases, organ/hematopoietic stem cell transplantation or other malignant tumors (except cured basal cell carcinoma of the skin and cervical carcinoma in situ).
* 3\. Patients with impaired consciousness or inability to cooperate with treatment, or patients with combined mental illness.
* 4\. Patients who have participated in other clinical trials in the last three months.
* 5\. Patients who have received other PD-1, PD-L1, CTLA-4 inhibitors in the past.
* 6\. Patients who have undergone major surgery or chemotherapy or other systemic or localized treatments (including but not limited to radiation therapy, ablation therapy, etc.) for the target lesion prior to enrollment.
* 7\. Use of interferon or systemic hormone therapy for immunosuppression within 14 days prior to enrollment (dose \>10mg/day prednisone or other equipotent hormone).
* 8\. Prior hypersensitivity to PD-1, PD-L1, CTLA-4 monoclonal antibody, any component of a chemotherapeutic agent, or other drugs of the same type used in the trial.
* 9\. Bleeding from ruptured esophageal (fundus) varices within 1 month prior to treatment.
* 10\. Uncorrectable coagulation dysfunction and serious blood abnormalities with severe bleeding tendency. Platelet count \<50×109/L and severe coagulation abnormality cannot withstand surgery (anticoagulation therapy and/or anticoagulant application should be discontinued for more than 1 week before radiation therapy).
* 11\. Intractable large amount of ascites and pleural fluid, malaise.
* 12\. Severe liver, kidney, heart, lung, brain and other major organ failure.
* 13\. Suffer from high blood pressure which cannot be reduced to normal range by antihypertensive drugs (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg).
* 14\. Previous severe cardiovascular disease, including but not limited to the following: myocardial ischemia or myocardial infarction of grade II or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men and ≥470 ms for women); cardiac insufficiency of grades Ⅲ to Ⅳ according to the NYHA standard or cardiac ultrasound suggesting that the left ventricular ejection fraction (LVEF) is \<50%.
* 15\. Patients with positive urine protein (urine protein test of 2+ or more, or 24-hour urine protein quantification \>1.0g).
* 16\. Inability to swallow tablets, malabsorption syndrome, or any condition that interferes with gastrointestinal absorption.
* 17\. Patients with other serious concomitant conditions that, in the judgment of the investigator, jeopardize patient safety or interfere with the patient's ability to complete the study.

Where this trial is running

Fuzhou, Fujian

• The First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China (RECRUITING)

Study contacts

• Principal investigator: Yufeng Chen — Zhangzhou Hospital of Fujian Medical University
• Study coordinator: Zhibo Zhang

Conditions: Biliary Tract Malignancies, biliary tract malignancies, neoadjuvant treatment, adebrelimab, apatinib, gemcitabine and cisplatin