Perioperative Treatment of Resectable Intrahepatic Cholangiocarcinoma With the Combination of Adebrelimab and Apatinib and HAIC

A Single Arm, Exploratory Clinical Study on the Perioperative Treatment of Resectable Intrahepatic Cholangiocarcinoma With the Combination of Adebrelimab and Apatinib and HAIC

The goal of this clinical trial is to explore the efficacy and safety of combined infusion chemotherapy with Adebrelimab and Apatinib in the perioperative treatment of resectable intrahepatic cholangiocarcinoma patients. The main question it aims to answer are:

How to improve the survival of patients with intrahepatic cholangiocarcinoma and prolong the recurrence time after surgery.

Participants will receive receive neoadjuvant therapy with Adebrelimab combined with apatinib and FOLFOX-HAIC for 2 cycles (1 treatment cycle every 21 days, apatinib only used for the first cycle), and surgery was performed 14-28 days after the end of treatment. After 28 days of surgery, patients will continue to receive adjuvant treatment with Adebrelimab combined with apatinib for a maximum of one year.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Procedure: HAIC; Drug: Adebrelimab; Drug: Apatinib

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital and Institute
      • Contact: Lei Zhao, MD; Phone Number: +86 053167626368; Email: drzhaolei@hotmail.com
      • Contact: Peifei Sun, MD; Phone Number: +86 053167626242
      • Principal Investigator: Lei Zhao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Pathological diagnosis as malignant tumor of Intrahepatic Cholangiocarcinoma;
• 2. According to the UICC/AJCC TNM staging system (8th edition, 2017), resectable subjects were classified as Ib-IIIb stages;
• 3. aged ≥ 18 years at the time of signing the Informed consent form (ICF);
• 4. Expected survival time>3 months;
• 5. Both men and women are eligible;
• 6. The patient's Eastern Oncology Collaborative Group (ECOG) physical condition score is 0 or 1;
• 7. No serious complications, such as hypertension, coronary heart disease, or history of mental illness, and no history of severe allergies; Non pregnancy and non lactation period;

• 8. The organ and blood system functions of the subjects meet the following requirements:

  1. Absolute neutrophil count (ANC) ≥ 1.5 × 10 ^ 9/L;
  2. Platelet count ≥ 75 × 10 ^ 9/L;
  3. Hemoglobin ≥ 90 g/L;
  4. Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN);
  5. Aspartate aminotransferase (AST) and alanine aminotransferase ≤ 2.5 x ULN;
  6. Albumin ≥ 3g/dL
  7. Creatinine ≤ 1.5 x ULN
• 9. The subjects can understand and sign the informed consent form to participate in the experimental study; Good compliance.
• 10. Participants who have not undergone any local or systemic treatment for tumors in the past, and have undergone radical resection surgery for biliary tract cancer before recurrence for at least 2 years, can be included;
• 11. Subjects with potential fertility need to use a medically approved contraceptive measure (such as an intrauterine device, contraceptive pill, or condom) during the study treatment period and within one month after the end of the study treatment period; And within 72 hours before enrollment, the serum or urine HCG test must be negative and must be non lactating;

Exclusion Criteria:

• 1. Patients who received PD-1, PD-L1, PD-L2, or CTLA-4 inhibitors before enrollment, or patients who directly received another stimulating or co inhibitory T cell receptor (such as CTLA-4, CD137);
• 2. Use any other investigational drugs within 4 weeks prior to enrollment;
• 3. Any history of active autoimmune diseases or autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism after hormone replacement therapy); Children with asthma who have completely improved in adulthood and do not require any intervention can be included, but patients who require intervention with bronchodilators cannot be included;
• 4. Congenital or acquired immunodeficiency, such as infection with human immunodeficiency virus (HIV), active hepatitis B (HBV DNA 500IU/ml), hepatitis C (hepatitis C antibody positive, HCV-RNA above the detection limit of the analysis method), or co infection with hepatitis B and hepatitis C;
• 5. Serious infection (such as intravenous infusion of antibiotics, antifungal or antiviral drugs) occurred within 4 weeks before the first administration, or unexplained fever>38.5 ° C occurred during screening/before the first administration;
• 6. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• 7. Suffering from uncontrollable mental illness;
• 8. The simultaneous occurrence of serious and/or uncontrollable diseases may affect the participation of the study, such as unstable angina pectoris, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, poorly controlled diabetes, serious activities, uncontrollable infection after insufficient biliary drainage (such as tumor blocking the bile duct);
• 9. Pregnancy (positive pregnancy test) or lactation period;
• 10. Other cancers that have occurred in the past (within the past 5 years) or simultaneously, excluding non melanoma skin cancer and in situ cancer;
• 11. History of allergy or hypersensitivity to any investigational drug;
• 12. Currently abusing alcohol or illegal drugs;
• 13. Unable or unwilling to sign informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC+Adebrelimab+apatinib; Neoadjuvant therapy with Adebrelimab combined with apatinib and FOLFOX-HAIC for 2 cycles (1 treatment cycle every 21 days, apatinib only used for the first cycle), and surgery was performed 14-28 days after the end of treatment. After 28 days of surgery, patients will continue to receive adjuvant treatment with Adebrelimab combined with apatinib.	Procedure: HAIC; FOLFOX-hepatic artery infusion for 2 times.; Drug: Adebrelimab; Adebrelimab 1200mg, ivgtt, d1, q3w,up to one year of use at most.; Drug: Apatinib; Apatinib 250mg, po, qd,q3w,up to one year of use at most.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR)	The proportion of subjects whose postoperative pathological examination did not detect residual cancer cells.	Up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate	Up to one year
Overall Survival (OS)	Overall Survival：The survival time from enrollment to death from any cause.	Up to two years
Disease Control Rate (DCR)	Disease Control Rate: Ratio of complete response (CR)+partial response (PR)+stable disease (SD)	Up to one year
Event free survival (EFS)	The time from enrollment to the scheduled occurrence of events, including death, disease recurrence, disease progression, etc	Up to two years

Collaborators and Investigators

• Sponsor: Lei ZHAO

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Actual): March 6, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: SHR1316-ICC-SD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No