Clinical trial NCT06181032: A Study of Adebrelimab in Combination With Apatinib Gemcitabine and Cisplatin in Biliary Tract Malignancies
Official title: A Single-arm Prospective Clinical Study of Adebrelimab in Combination With Apatinib Gemcitabine and Cisplatin for the Neoadjuvant Treatment of Biliary Tract Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Biliary Tract Malignancies
Keywords: biliary tract malignancies
neoadjuvant treatment
adebrelimab
apatinib
gemcitabine and cisplatin
Lead sponsor: First Affiliated Hospital of Fujian Medical University
Sponsor class: OTHER
First posted: 2023-12-26
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluating the efficacy and safety of adebrelimab in combination with apatinib, gemcitabine and cisplatin in the neoadjuvant treatment of patients with biliary tract malignancies.

Detailed description: Existing immune-combination chemotherapy has shown excellent data in advanced biliary malignancies, so what is the efficacy and safety of this regimen in neoadjuvant therapy? Moreover, the current combination model of immunization combined with anti-angiogenic drugs has become another new direction in the field of solid tumor treatment. Therefore, our group designed a single-arm, prospective clinical study of adebrelimab in combination with apatinib, gemcitabine and cisplatin in the neoadjuvant treatment of biliary malignancies, aiming at evaluating the efficacy and safety of adebrelimab in combination with apatinib, gemcitabine and cisplatin in the neoadjuvant treatment of biliary malignancies in patients with a view to bringing longer-term benefits to patients with resectable biliary malignancies.

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.

Primary outcomes:
measure: Relapse free survival（RFS）
timeFrame: 3 years
measure: AE
timeFrame: 3 years
Secondary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: Within one week after surgery
measure: Major pathological response rate (MPR)
timeFrame: Within one week after surgery
measure: surgery rate
timeFrame: Within one week after surgery
measure: Radical (R0) resection rate
timeFrame: Within one week after surgery
measure: Objective response rate (ORR)
timeFrame: Within 2 weeks prior to surgery
measure: Disease control rate (DCR)
timeFrame: Within 2 weeks prior to surgery
measure: Overall survival (OS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
Study officials:
affiliation: Zhangzhou Hospital of Fujian Medical University
name: Yufeng Chen
role: PRINCIPAL_INVESTIGATOR
affiliation: Fujian Provincial Hospital
name: Maolin Yan
role: PRINCIPAL_INVESTIGATOR
References: