Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil for Advanced Cholangiocarcinoma

Second-line Treatment of PD-1 and CTLA-4 Blockade Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil for Advanced Cholangiocarcinoma: a Single-arm, Prospective Phase II Trial

This study aimed to evaluate the efficacy and safety of the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin for the treatment of advanced biliary tract cancer.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Combination product: Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dan Cao; Phone Number: 86-28-85422589; Email: caodan@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Dan Cao; Phone Number: 86-28-85422589; Email: caodan@scu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosed with pathologically confirmed locally advanced unresectable or metastatic adenocarcinoma of the bile ducts, gallbladder, or cholangiocellular carcinoma, with primary tumors located in the intrahepatic bile ducts, hilar bile ducts, distal bile ducts, or gallbladder;
2. Progression after prior gemcitabine-based systemic chemotherapy and refused or were intolerable to initial treatment with gemcitabine-based chemotherapy regimens;
3. At least one measurable objective lesion of the tumor according to the RECIST version 1.1 criteria, which must have a maximum diameter of ≥1 cm for spiral CT or ≥2 cm for plain CT or MRI; and should be performed within 28 days prior to enrollment;
4. Aged 18 to 75 years old;
5. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1;
6. Life expectancy of greater than 3 months;
7. Must be able to participate the study voluntarily and sign the informed consent document;
8. Adequate organ and bone marrow function as below:

Absolute neutrophil count ≥1.5*109/L , platelet count ≥75*109/L , hemoglobin ≥90g/L; Alanine aminotransferase, and aspartate aminotransferase ≤2.5 × upper limit of normal; Total bilirubin and serum creatinine ≤1.5 × upper limit of normal.

Exclusion Criteria:

1. Disease-free survival within 5 years due to other malignancies (except for adequately treated basal cell carcinoma of the skin and carcinoma in situ of the cervix);
2. Serious or uncontrolled infectious disease (HIV, HBV DNA > 500IU/ml);
3. Severe uncontrolled acute infection (infection causing a fever of 38℃ or higher)；
4. Severe hepatic or renal insufficiency; or recent history of myocardial infarction (within 3 months)；
5. Current or past autoimmune disease and susceptibility to its reoccurrence;
6. Serious or uncontrolled pleural effusion or ascites;
7. Subjects with a history of active tuberculosis infection within 1 year prior to the first administration of study drug. If in the judgment of the investigator, subjects with more than 1 year prior to the first administration of study drug were considered suitable for enrollment; Subjects with a long history of chronic diarrhea or the presence of complete intestinal obstruction;
8. Subjects requiring systemic therapy with corticosteroids (> 10 mg/day prednisone equivalent dose) or other immunosuppressive drugs within 14 days prior to administration of study drug.
9. Combined with other serious medical and surgical conditions that affected organ function;
10. Participated in other clinical trial within 4 weeks;
11. Pregnant or breastfeeding women or subjects of childbearing potential (males or females with less than 1 year of menopause) who were unwilling to use contraception;
12. Subjects with a history of allergic or hypersensitivity reactions to components of the study drug;

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: Cadonilimab+NIFU regimen; There will be two cohorts. Cohort 1 includes patients who have failed first-line treatment with gemcitabine-based chemotherapy combined with PD-L1/PD-1 monoclonal antibody immunotherapy. Cohort 2 includes patients who have failed chemotherapy with gemcitabine-based chemotherapy as a first-line treatment and who had not been treated with PD-L1/PD-1 monoclonal antibody immunotherapy.

Combination product: Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil; cadonilimab at a dosage of 6 mg/kg on day 1 combined with intravenous liposomal irinotecan at a dosage of 70 mg/m2 for 90 min on day 1 plus leucovorin at a dosage of 400 mg/m2 for 30 min on day 1 and fluorouracil at a dosage of 2400 mg/m2 for 46 h every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate (ORR)	The total number of participants in the intention-to-treat (ITT) population who achieve a complete response (CR) or partial response (PR) will be considered valid, and the statistical results were used to calculate the ORR based on imaging (CT/MRI) using the RECIST v1.1 criteria.	Up to 2 years

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: May 27, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Irinotecan; Fluorouracil; Leucovorin
• Other Study ID Numbers: 2024（791）

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