Adebrelimab Combined with Irinotecan Liposomes, 5-FU, CF ± Lenvatinib As First-line Treatment for Advanced ICC

Adebrelimab Combined with Irinotecan Liposomes, 5-fluorouracil, Calcium Folinate ± Lenvatinib As First-line Treatment for Advanced Intrahepatic Cholangiocarcinoma: a Prospective Clinical Study

This is a multicenter, open label, randomized, two-arm clinical study to observe and evaluate the efficacy and safety of adebrelimab combined with irinotecan liposomes, 5-fluorouracil, calcium folinate ± lenvatinib as first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).

Study Overview

• Status: Not yet recruiting
• Conditions: Intrahepatic Cholangiocarcinoma (Icc)
• Intervention / Treatment: Drug: Adebrelimab; Drug: Irinotecan liposomes; Drug: Lenvatinib; Drug: 5-Fluorouracil (5-FU); Drug: Calcium Folinate

Detailed Description

This study plans to recruit 68 patients with unresectable ICC who have not received prior systematic treatment. The patients will be randomly divided into two groups. Group A: patients will receive adebrelimab+irinotecan liposomes+5-fluorouracil+calcium folinate+lenvatinib; Group B: patients will receive treatment with adebrelimab+irinotecan liposomes+5-fluorouracil+calcium folinate. The combination of irinotecan liposomes+5-fluorouracil+calcium folinate will be used 9 times (Q2W), and adebrelimab ± lenvatinib will be used until disease progression or medication for 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiwei Li, MD; Phone Number: 86+15004683651; Email: lzhw0451@163.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University
      • Contact: Zhiwei Li, MD; Phone Number: 86+15004683651; Email: lzhw0451@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: 18 to 75 years old, male or female not limited;
2. Histologically confirmed unresectable locally advanced or metastatic intrahepatic cholangiocarcinoma with measurable tumor lesions (meeting RECIST 1.1 criteria);
3. Have not received systemic anti-tumor treatment in the past;
4. Patients who relapse more than 6 months after curative surgery or after completion of adjuvant therapy (chemotherapy and/or radiotherapy) meet the inclusion criteria;
5. ECOG PS：0-1；
6. Expected survival period ≥ 3 months;
7. The main organ functions are normal, which meets the following criteria:

1) Blood routine examination (without blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days): Hemoglobin (Hb) ≥ 85 g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 80 × 109/L; 2) Biochemical examination: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN; Serum total bilirubin (TBIL) ≤ 3 × ULN; Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate ≥ 50ml/min; 3) Coagulation function: Activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN; 4) Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥ 50%; 8. Women of childbearing age must undergo a negative pregnancy test (β HCG) before starting treatment, and women and men of childbearing age (who have sexual relations with women of childbearing age) must agree to continuously use effective contraceptive measures during the treatment period and for 6 months after the last treatment dose; 9. Patients with a history of hepatitis B and C can be included in the study, but active hepatitis B patients must start antiviral therapy before starting the study treatment; 10. Participants voluntarily join the study and sign an informed consent form.

Exclusion Criteria:

1. Pregnant or lactating women, or those who have the ability to conceive but refuse to take contraceptive measures;
2. History of other malignant tumors within the past 5 years, excluding cervical carcinoma in situ or squamous cell carcinoma of the skin that has been adequately treated, or basal cell carcinoma of the skin that has been largely controlled;
3. Merge other serious uncontrolled diseases (such as individuals with a history of difficult to control mental illness or severe intellectual or cognitive impairment; severe heart failure, angina pectoris, myocardial infarction, arrhythmia, etc.);
4. Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function;
5. Suffering from active, known or suspected autoimmune diseases. Subjects with hypothyroidism who only require hormone replacement therapy and those with skin diseases that do not require systemic treatment may be included;
6. Easy to bleed, at risk of massive hemoptysis, and with a history of significant coagulation dysfunction;
7. Suffering from hypertension and unable to achieve good control with antihypertensive medication (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg);
8. History of immunodeficiency, including HIV testing positive, having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation and allogeneic bone marrow transplantation;
9. Severe active infections requiring intravenous antibiotic treatment occur during the screening period;
10. Individuals with multiple factors that affect oral medication (such as inability to swallow, post gastrointestinal resection, chronic diarrhea, and intestinal obstruction);
11. Individuals who are allergic to the experimental drug;
12. Patients who cannot comply with the trial protocol or cooperate with follow-up;
13. The researchers believe that participants should not participate in this experiment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Adebrelimab+Irinotecan liposomes+5-fluorouracil+calcium folinate+lenvatinib; Adebrelimab in combination with Irinotecan liposomes, 5-fluorouracil, calcium folinate and lenvatinib	Drug: Adebrelimab; Adebrelimab, IV; Drug: Irinotecan liposomes; Irinotecan liposomes, IV; Drug: Lenvatinib; Lenvatinib, po; Drug: 5-Fluorouracil (5-FU); 5-Fluorouracil (5-FU), IV; Drug: Calcium Folinate; Calcium folinate, IV
Experimental: Group B: Adebrelimab+Irinotecan liposomes+5-fluorouracil+calcium folinate; Adebrelimab in combination with Irinotecan liposomes, 5-fluorouracil and calcium folinate	Drug: Adebrelimab; Adebrelimab, IV; Drug: Irinotecan liposomes; Irinotecan liposomes, IV; Drug: 5-Fluorouracil (5-FU); 5-Fluorouracil (5-FU), IV; Drug: Calcium Folinate; Calcium folinate, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free-Survival (PFS)	The time from enrollment until tumor progression or death from any cause, whichever occurred first	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The proportion of patients with a PR or CR, determined by RECIST v1.1 criteria	up to 24 months
Disease control rate (DCR)	The proportion of patients with a PR, CR, or SD	up to 24 months
Overall survival (OS)	The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date	up to 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Incidence and severity of adverse events graded according to the NCI CTCAE v5.0.	up to 24 months

Collaborators and Investigators

• Sponsor: Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Lenvatinib; Intrahepatic Cholangiocarcinoma; Adebrelimab; Irinotecan liposomes
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Protein Kinase Inhibitors; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Calcium; Levoleucovorin; Lenvatinib
• Other Study ID Numbers: MA-ICC-II-006

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
• product manufactured in and exported from the U.S.: No