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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• overall response rate (ORR) [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• 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;
• Progression after prior gemcitabine-based systemic chemotherapy and refused or were intolerable to initial treatment with gemcitabine-based chemotherapy regimens;
• 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;
• Aged 18 to 75 years old;
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1;
• Life expectancy of greater than 3 months;
• Must be able to participate the study voluntarily and sign the informed consent document;
• 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

• 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);
• Serious or uncontrolled infectious disease (HIV, HBV DNA > 500IU/ml);
• Severe uncontrolled acute infection (infection causing a fever of 38℃ or higher)；
• Severe hepatic or renal insufficiency; or recent history of myocardial infarction (within 3 months)；
• Current or past autoimmune disease and susceptibility to its reoccurrence;
• Serious or uncontrolled pleural effusion or ascites;
• 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;
• 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.
• Combined with other serious medical and surgical conditions that affected organ function;
• Participated in other clinical trial within 4 weeks;
• 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;
• Subjects with a history of allergic or hypersensitivity reactions to components of the study drug;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• West China Hospital, Sichuan University — Chengdu

Publications

• Yang H, Li L, Li X, Ma Y, Yang Y, Cao D. Second-line treatment of PD-1 and CTLA-4 blockade combined with liposomal irinotecan plus leucovorin and fluorouracil for advanced cholangiocarcinoma: study protocol of a single-arm, prospective phase II trial. Ther Adv Med Oncol. 2024 Oct 28;16:17588359241292264. doi: 10.1177/17588359241292264. eCollection 2024. PMID 39492841

Identifiers

NCT: NCT06438822 · 2024（791）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗