The Safety and Efficacy of CD-801 in Patients With Advanced Intrahepatic Cholangiocarcinoma

The Safety and Efficacy of Transarterial Injection of CD-801 in Patients With Advanced Intrahepatic Cholangiocarcinoma

The goal of this clinical trial is to learn about the safety of CD-801, a lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4α (HNF4α) in treating patients with advanced intrahepatic cholangiocarcinoma (ICC). It will also learn if CD-801 works to treat advanced ICC. The main questions it aims to answer are:

1. What medical problems do participants have when injecting CD-801?
2. Is CD-801 effective for ICC patients according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or modified RECIST (mRECIST)

Participants will:

Receive administration of 100μg of CD-801 via hepatic arterial injection every 14 ± 3 days (the dosing interval will be adjusted based on the tolerability, safety, and therapeutic effect of the subjects), for one treatment cycle. Treatment will continue until the occurrence of disease progression, death, intolerable toxicity, voluntary withdrawal of informed consent, loss to follow-up, initiation of new antitumor treatment, or termination of the study by the investigator (whichever comes first), and completion of the final follow-up and assessment 14 days after the last administration.

Study Overview

• Status: Withdrawn
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Genetic: Injection of CD-801, a lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4α (HNF4α)

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Wen-Ping Xu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males or females, aged 18 years or older.
• Histologically or cytologically confirmed intrahepatic cholangiocarcinoma patients.
• Patients with intrahepatic cholangiocarcinoma not suitable for surgical resection, liver transplantation, or ablation therapy, or those with post-surgical recurrence and/or metastasis.
• Patients not suitable for local or systemic treatment, or those who have progressed after at least one chemotherapy regimen containing gemcitabine/fluoropyrimidine/platinum, etc..
• Life expectancy of 12 weeks or more.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
• Males with fertility and females of childbearing potential are willing to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation. Females of childbearing age, including premenopausal females and within 2 years after menopause, must have a negative serum pregnancy test result within 7 days prior to the first dose of study treatment.
• Subjects who had a voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

Exclusion Criteria:

• Patients with any of the following criteria were excluded from participation in this study:

  • Inadequate liver function：Albumin (ALB) < 25 g/L, or total bilirubin > 5 × the upper limit of normal (ULN), or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) >10 × ULN.
  • Inadequate renal function defined as creatinine >1.5 × ULN or calculated creatinine clearance < 40 mL/min.
  • Absolute neutrophil count (ANC) < 1.0×109/L, or Platelets < 30×109/L, or Hemoglobin < 8.5 g/dL.
  • International normalized ratio (INR) > 2.3.
  • Poorly controlled hypertension, diabetes or other serious heart or lung diseases, or with serious dysfunction.
  • Patients who have received local or systemic anti-tumor treatments such as ablation, Transhepatic Arterial Chemotherapy and Embolization (TACE), local radiotherapy of the liver, immunotherapy, targeted therapy, etc., within 4 weeks, or chemotherapy, other trial drugs, or radiotherapy of metastatic lesions within 2 weeks, except for treatment regimens assessed as disease progression according to mRECIST or RECIST 1.1.
  • Patients with uncurable brain metastasis.
  • All toxicities related to prior locoregional or systemic anti-tumor treatments are still grade 2 or more (except for hair loss and other events that have been judged tolerable by researchers).
  • Complication histories of liver cirrhosis or HCC such as gastrointestinal hemorrhage, overt hepatic encephalopathy, or refractory ascites within 2 weeks prior to the first dose of study treatment.
  • Uncontrolled active infection (eg, lung infections, or abdominal infections).
  • History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated early gastric carcinoma, carcinoma in situ of the cervix, non-melanoma skin carcinoma, or localized prostate cancer.
  • Hepatitis B virus DNA greater than 500 copies/mL, or hepatitis C virus RNA greater than 15 U/mL.
  • Positive for human immunodeficiency virus (HIV).
  • Allergic to contrast agents.
  • Pregnant/lactating women, or women with the possibility of pregnancy.
  • Any medical conditions which, in the opinion of the investigator, would preclude participation in this clinical trial.

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: CD-801, a lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4α; Patients will receive administration of 100μg of CD-801 via hepatic arterial injection every 14 ± 3 days

Genetic: Injection of CD-801, a lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4α (HNF4α); Receive administration of 100μg of CD-801 via hepatic arterial injection every 14 ± 3 days (the dosing interval will be adjusted based on the tolerability, safety, and therapeutic effect of the subjects), for one treatment cycle. Treatment will continue until the occurrence of disease progression, death, intolerable toxicity, voluntary withdrawal of informed consent, loss to follow-up, initiation of new antitumor treatment, or termination of the study by the investigator (whichever comes first), and completion of the final follow-up and assessment 14 days after the last administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The incidence, timing, and severity of adverse events, serious adverse events, and adverse events leading to treatment discontinuation according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The proportion of subjects achieving Complete Response (CR) and Partial Response (PR).	up to 24 months
Duration Of Response	The time from the first documentation of response (either Partial Response or Complete Response) after the start of treatment to the first documentation of disease progression or death due to Intrahepatic Cholangiocarcinoma (ICC), whichever occurs first.	up to 24 months
Progression-Free Survival	The time from the start of treatment to the first occurrence of disease progression or death due to Hepatocellular Carcinoma (HCC), whichever comes first. The time from the initiation of treatment to the first documentation of disease progression or death due to Intrahepatic Cholangiocarcinoma (ICC), whichever occurs first.	From date of the start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Time To Progression	The time from the start of treatment to the first recorded documentation of disease progression, excluding death.	up to 24 months
Time To Response	The time from the commencement of treatment to the first documentation of response achieving either Partial Response (PR) or Complete Response (CR).	up to 24 months
Disease Control Rate	The proportion of subjects achieving response with either Partial Response (PR) or Complete Response (CR), or maintaining stable disease (SD with duration of ≥ 5 weeks) after treatment.	up to 24 months
Clinical Benefit Rate	The proportion of subjects who achieve either a Partial Response (PR) or Complete Response (CR) following treatment, or maintain durable stable disease (SD with a duration of at least 23 weeks).	up to 24 months
Overall Survival	The time from the start of treatment to death from any cause.	From date of the start of treatment until the date of death from any cause, assessed up to 36 months
Patient Reported Outcome-1	the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	up to 24 months
Patient Reported Outcome-2	the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BIL21 (QLQ-BIL21)	up to 24 months
Patient Reported Outcome-3	The Generic Euroquol Five Dimension Five Level (EQ-5D-5L) Questionnaire	up to 24 months
The changes in tumor markers after treatment.	The changes in tumor markers such as CA19-9, Carcinoembryonic Antigen (CEA), and Alpha-fetoprotein (AFP) after treatment.	up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 28, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 24, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma
• Other Study ID Numbers: 2024SL015

Drug and device information, study documents

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