A Study of Adebrelimab in Combination With Apatinib Gemcitabine and Cisplatin in Biliary Tract Malignancies

Phase 1

Recruiting

• Conditions: Biliary Tract Malignancies
• Interventions: Drug: Adebrelimab; Drug: Apatinib; Drug: Gemcitabine; Drug: Cisplatin

• Registration Number: NCT06181032
• Lead Sponsor: First Affiliated Hospital of Fujian Medical University

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.

Study Timeline

• Study First Submitted: 2023-11-23
• Study First Submitted QC: 2023-12-21
• Study Start: 2023-12-23
• Study First Posted: 2023-12-26
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-27
• Last Update Posted: 2024-04-30
• Primary Completion: 2029-02-23
• Study Completion: 2029-02-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm	Cisplatin	Neoadjuvant treatment with adebrelimab in combination with apatinib gemcitabine and cisplatin
Single arm	Adebrelimab	Neoadjuvant treatment with adebrelimab in combination with apatinib gemcitabine and cisplatin
Single arm	Apatinib	Neoadjuvant treatment with adebrelimab in combination with apatinib gemcitabine and cisplatin
Single arm	Gemcitabine	Neoadjuvant treatment with adebrelimab in combination with apatinib gemcitabine and cisplatin

Primary Outcome Measures

Name	Time	Method
Relapse free survival（RFS）	3 years	Means the time from the date of the curative surgery to the date of relapse or death.
AE	3 years	Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Secondary Outcome Measures

Name	Time	Method
Pathological complete response rate (pCR)	Within one week after surgery	Rate of residual tumor cells not detected by pathology in excised tissue samples.
Disease control rate (DCR)	Within 2 weeks prior to surgery	Refers to the proportion of all subjects with a best overall result (BOR) of complete remission (CR), partial remission (PR), and stable disease (SD) as rated according to RECIST 1.1 criteria.
Objective response rate (ORR)	Within 2 weeks prior to surgery	Refers to the proportion of all subjects with a best overall result (BOR) of complete remission (CR) or partial remission (PR) as rated according to RECIST 1.1 criteria. If efficacy of CR or PR is achieved, subjects must be confirmed not less than 4 weeks ± 7 days after the initial evaluation.
Major pathological response rate (MPR)	Within one week after surgery	The percentage of active tumor cells in excised tissue samples is less than 10% of the rate.
surgery rate	Within one week after surgery	Proportion of patients with final surgical resection among enrolled surgically resectable patients.
Radical (R0) resection rate	Within one week after surgery	No residual cancer cells on the margins
Overall survival (OS)	5 years	Defined as the time between the date of first dose and the death of the subject due to all causes. Subjects who were alive at the last follow-up visit had OS counted as data censored at the time of the last follow-up visit. The OS of subjects who were lost to follow-up was counted as data censored at the time of last confirmed survival prior to the lost follow-up. OS for data censoring was defined as the time from first dose to censoring.

Trial Locations

Locations (1)

The First Affiliated Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China