Phase II Clinical Study on the Efficacy and Safety of the Combination of Cadonilimab and Capecitabine in Adjuvant Therapy for Combined Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

NCT07243951 | Not Yet Recruiting Phase 2

• 1 other identifier: B2025-381R
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

Title: A Study of Cadonilimab Combined with Capecitabine After Surgery for Mixed Type Liver Cancer This is a phase II clinical trial. The main purpose of this study is to find out if using two drugs together, cadonilimab (an immunotherapy drug) and capecitabine (a chemotherapy drug), can help prevent the cancer from coming back after surgery in patients with a specific type of liver cancer called combined hepatocellular-cholangiocarcinoma (cHCC/CCA). This type of liver cancer is rare and has a high chance of returning even after successful surgery. The study will involve about 75 patients who have had their tumor completely removed but are still at medium to high risk of the cancer returning. All participants in the study will receive the same combination of drugs. Cadonilimab is given through a vein every three weeks. Capecitabine is taken as a pill twice a day for two weeks, followed by one week off. This cycle repeats for up to 8 cycles (about 6 months), or until the cancer comes back or side effects become too severe. Researchers will primarily measure how long patients live without the cancer returning (Recurrence-Free Survival). They will also track how long patients live overall (Overall Survival), and carefully record any side effects to understand the safety of this treatment combination. The study hypothesis is that this combination therapy will significantly prolong RFS compared to historical outcomes with surgery alone, while demonstrating acceptable safety.

Conditions

Combined Hepatocellular-cholangiocarcinoma; Liver Neoplasms

Keywords

Cadonilimab; Capecitabine; Phase II Clinical Trial; Bispecific Antibody; PD-1; CTLA-4; Recurrence-Free Survival; Immunotherapy; Adjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Recurrence-Free Survival (RFS)

  The length of time after primary treatment for cancer ends that the patient survives without any signs or symptoms of that cancer. Tumor recurrence or metastasis will be determined based on radiological imaging (CT or MRI) and evaluated according to RECIST 1.1 criteria.

  From the start of treatment until the date of first documented recurrence, metastasis, or death from any cause.ssessed regularly every 12 weeks (every 4 cycles) during treatment, then every 12 weeks until 24 months after treatment completion.

Secondary Outcomes (2)

• Overall Survival (OS)

  From the start of treatment until the date of death from any cause, assessed every 3 months (±14 days) until 24 months after treatment completion.

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  up to 2 years

Other Outcomes (1)

• PD-L1 Expression Level in Tumor Tissue

  Assessed at baseline (using archival tumor tissue obtained during prior surgical resection).

Study Arms (1)

Cadonilimab + Capecitabine Combination Therapy

EXPERIMENTAL

This arm receives the combination therapy of Cadonilimab (intravenous infusion, 10 mg/kg, once every 3 weeks) and Capecitabine (oral, 2500 mg/m²/day administered in two divided doses, on a schedule of 2 weeks of treatment followed by 1 week of rest) for up to 8 cycles (24 weeks), or until disease recurrence, unacceptable toxicity, or other treatment discontinuation criteria are met.

Drug: Cadonilimab; Drug: Capecitabine

Interventions

Cadonilimab DRUG

Cadonilimab is a bispecific monoclonal antibody targeting both PD-1 and CTLA-4. It will be administered intravenously at a dose of 10 mg/kg over 60-120 minutes (no less than 60 minutes) on Day 1 of each 3-week cycle.

Cadonilimab + Capecitabine Combination Therapy

Capecitabine DRUG

Capecitabine is an oral chemotherapeutic prodrug that is converted to 5-fluorouracil in the body. The dose is 2500 mg/m² per day, administered orally in two divided doses (morning and evening) within 30 minutes after a meal. It is given for 2 weeks followed by a 1-week rest, constituting one 3-week cycle.

Cadonilimab + Capecitabine Combination Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years.
• ECOG Performance Status ≤ 1.
• Pathologically confirmed combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC/CCA), with R0 resection and classified as Stage IB, Stage II, Stage IIIA, Stage IIIB, or Stage IA (G3) according to AJCC TNM Staging System (8th Edition, 2017).
• No extrahepatic metastasis.
• Post-operative Child-Pugh liver function class A; ECOG PS score: 0-1.
• For subjects with chronic HBV infection, HBV-DNA must be \<500 IU/mL. HBsAg-positive patients must receive antiviral therapy according to the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2015)". HCV-RNA positive patients must receive antiviral therapy according to the "Guidelines for the Prevention and Treatment of Hepatitis C (2015)" and have normal liver function.
• Adequate organ function, defined as follows:
• (1) Hematological tests (no blood transfusion or use of hematopoietic growth factors within 14 days prior to screening):
• Hemoglobin (HB) ≥90 g/L
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• Platelet count (PLT) ≥75×10⁹/L (2) Biochemical tests (no blood transfusion or blood products within 14 days prior to screening):
• \) Albumin (ALB) ≥29 g/L 2) ALT and AST \<2.5 × ULN 3) Total bilirubin (TBIL) ≤1.5 × ULN 4) Creatinine (Cr) ≤1.5 × ULN (3) International Normalized Ratio (INR) ≤2.3, or Prothrombin Time (PT) prolongation ≤6 seconds beyond the normal control range.
• \. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days before initiating study treatment and be willing to use effective and reliable methods of contraception during the trial and for one year after the last dose of the study drug.
• \. Subjects voluntarily join the study, sign the informed consent form, have good compliance, and are willing to cooperate with follow-up.
• \. No evidence of tumor recurrence or metastasis at baseline examination.

You may not qualify if:

• Pathological diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or hilar cholangiocarcinoma.
• Incomplete tumor resection (non-R0), or postoperative pathology indicating a diagnosis other than cHCC/CCA.
• History of or concurrent other malignancies, except for cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc. Concurrent autoimmune diseases (e.g., autoimmune liver disease, systemic lupus erythematosus).
• Child-Pugh class B or C; history or presence of manifestations of hepatic decompensation (e.g., ascites, hepatic encephalopathy, upper gastrointestinal bleeding, etc.).
• Known hereditary or acquired bleeding or thrombotic tendencies, such as hemophilia.
• Presence of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 2 months prior to study participation.
• Myocardial ischemia of grade II or above, myocardial infarction, or poorly controlled arrhythmias (including QTcF interval ≥450 ms for males or ≥470 ms for females; QTc interval calculated by Fridericia's formula). Cardiac insufficiency of NYHA Class III-IV or left ventricular ejection fraction (LVEF) \<50% on echocardiography.
• Severe cardiopulmonary dysfunction or severe renal insufficiency.
• History of thrombotic/embolic events within the past 6 months, such as cerebrovascular events (including transient ischemic attack) or pulmonary embolism.
• Inability to swallow, chronic diarrhea, or intestinal obstruction that significantly affects drug administration and absorption.
• Untreated active hepatitis (Hepatitis B: HBsAg positive with abnormal liver function and HBV-DNA ≥500 IU/mL; Hepatitis C: HCV-RNA positive with abnormal liver function).
• Human Immunodeficiency Virus (HIV) infection.
• Active infection or unexplained fever (\>38.5°C) occurring during the screening period or before the first dose.
• Receipt of any vaccine within 30 days prior to enrollment. Planned or prior history of allogeneic organ or bone marrow transplantation, including liver transplantation.
• History or current presence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired pulmonary function, or other conditions that may interfere with the detection and management of suspected drug-related pulmonary toxicity.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Liver Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Qiang GAO, Doctor

CONTACT

086-021-64041990-2047; gaoqiang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: November 28, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-11