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

NCT ID: NCT06181032

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-23
• Study Completion Date: 2029-02-23

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.

Conditions

Biliary Tract Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

Neoadjuvant treatment with adebrelimab in combination with apatinib gemcitabine and cisplatin

Group Type: EXPERIMENTAL

Adebrelimab

Intervention Type: DRUG

Adebrelimab: 1200mg or 20mg/kg, iv, D1, Q3W;

Apatinib

Intervention Type: DRUG

Apatinib: 250 mg, po, QD, Q3W;

Gemcitabine

Intervention Type: DRUG

Gemcitabine: 1000 mg/m2, iv, 30min, D1, D8, Q3W;

Cisplatin

Intervention Type: DRUG

Cisplatin: 25 mg/m2, iv, 30min, D1, D8, Q3W; Injection sequence: adebelizumab → gemcitabine → cisplatin (sequential interval of at least 30 min), 3 cycles of neoadjuvant therapy.

Interventions

Adebrelimab

Adebrelimab: 1200mg or 20mg/kg, iv, D1, Q3W;

Intervention Type: DRUG

Apatinib

Apatinib: 250 mg, po, QD, Q3W;

Intervention Type: DRUG

Gemcitabine

Gemcitabine: 1000 mg/m2, iv, 30min, D1, D8, Q3W;

Intervention Type: DRUG

Cisplatin

Cisplatin: 25 mg/m2, iv, 30min, D1, D8, Q3W; Injection sequence: adebelizumab → gemcitabine → cisplatin (sequential interval of at least 30 min), 3 cycles of neoadjuvant therapy.

Intervention Type: DRUG

Other Intervention Names

SHR-1316

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Fujian Medical University

OTHER

Sponsor Role: lead

Responsible Party

Zhang Zhibo

Director of Hepatobiliary and Pancreatic Surgery Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yufeng Chen

Role: PRINCIPAL_INVESTIGATOR

Zhangzhou Hospital of Fujian Medical University

Maolin Yan

Role: PRINCIPAL_INVESTIGATOR

Fujian Provincial Hospital

Locations

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhibo Zhang

Role: CONTACT

zbzhang_1234@163.com

13960986516

Facility Contacts

Zhang Zhibo, PhD

Role: primary

wql0211@gmail.com

008618559853003

Other Identifiers

23-OBU-FJ-BTC-II-001

Identifier Type: -

Identifier Source: org_study_id