Trial Title:
A Clinical Trial Evaluating the Safety and Efficacy of Intravenous CD-801 in Treating Advanced HCC Patients
NCT ID:
NCT06418659
Condition:
Advanced Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Conditions: Keywords:
Hepatocellular carcinoma
Hepatocyte nuclear factor 4α
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
The subjects with advanced HCC will be treated by CD-801 intravenously via a peripheral
vein.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CD-801
Description:
CD-801 will be administered intravenously for the treatment of HCC. The dosing regimen is
planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent
treatments every 28 ± 7 days, with adjustments made based on patient tolerance and
therapeutic response.
Arm group label:
CD-801 treatment
Summary:
The goal of this investigator-initiated, a single-arm, open-label, pilot study is to
investigate the safety, tolerability, and efficacy of Intravenous CD-801 treatment in
subjects with advanced hepatocellular carcinoma(HCC).
Condition of disease: advanced hepatocellular carcinoma.
Intervention： CD-801 will be administered intravenously for the treatment of HCC. The
dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed
by subsequent treatments every 28 ± 7 days, with adjustments made based on patient
tolerance and therapeutic response. The trial is structured in two phases: dose
escalation and dose expansion.
Dose Escalation Phase:
The study employs a i3+3 design to assess escalating CD-801 dosages: 25 μg, 50 μg, and
100 μg. Post-initial dose, a 14-day DLT observation will evaluate tolerability and
safety, guiding dose adjustments or selection of the Recommended Dose (RD) for the
expansion phase. Cohorts may include up to 9 participants, adjusted for safety.
Dose Expansion Phase:
The expansion phase will use the safe dosage and regimen from the escalation phase, with
treatments starting 14 ± 3 days after the initial dose, then every 28 ± 7 days, adjusted
as needed. It ends upon complete response, disease progression, toxicity, withdrawal,
loss to follow-up, new oncological treatments, or investigator termination, with a final
assessment 14 days post-last dose. The phase plans to enroll about 10 participants to
further assess CD-801's safety, tolerability, and antitumor effects using mRECIST.
Drug: CD-801, a drug specifically designed to target liver cancer cells and facilitate
the expression of HNF4α.
Detailed description:
Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Recent
advancements in understanding tumor biology and the tumor microenvironment, along with
the approval of systemic therapeutic agents, including immunotherapy and vascular
endothelial growth factor (VEGF)-targeted agents, have dramatically transformed the
treatment landscape for advanced stage HCC. However, the survival for advanced HCC
patients still remains unsatisfactory.
Differentiation therapy in oncology is defined as a therapeutic strategy that reactivates
endogenous differentiation programs and reverts malignant phenotypes. Its hallmark
success is the treatment of acute promyelocytic leukemia (APL) by the combination of
all-trans retinoic acid (ATRA) and arsenic. Unfortunately, this approach has achieved
limited success in solid tumors.
Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor (TF) belonging to the
nuclear receptor family. HNF4α is highly enriched in mature hepatocytes and serves as a
master regulator of hepatocyte differentiation and hepatic metabolism. Previous studies,
including our own and others, have demonstrated that the reduced expression of HNF4α
plays a critical role in hepatocarcinogenesis. Restoring HNF4α expression induces the
differentiation of HCC cells into mature hepatocytes and has shown significant
therapeutic effects in various animal models of HCC.
In this study, the investigators developed CD-801, a drug specifically designed to target
liver cancer cells and facilitate the expression of HNF4α, for the treatment of HCC
patients. Preclinical studies have shown that CD-801 effectively inhibits the growth of
subcutaneous and orthotopic liver tumors in mice. Acute toxicity tests in Sprague-Dawley
rats have demonstrated that a single intravenous injection of CD-801 injection at a dose
of 150 μg/animal is well-tolerated, with no significant toxicity, indicating good safety
profiles.
This trial, structured in two phases: dose escalation and dose expansion, is a
single-arm, open-label, exploratory clinical study aimed at evaluating the efficacy,
safety, and tolerability of CD-801 administered intravenously through a peripheral vein
in the treatment of advanced-stage HCC. The treatment schedule is planned for a second
dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7
days, with adjustments made based on patient tolerance and therapeutic response.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males or females, aged 18 years or older.
2. Subjects must have confirmed diagnosis of HCC with any of the following criteria
according to the American Association for the Study of Liver Diseases criteria.
3. Unresectable HCC.
4. Subjects were not eligible for locoregional or systemic therapies, or had disease
progression, or would not benefit after at least one of the conventional therapies.
5. According to mRECIST, subjects should be with at least 1 measurable target lesion.
6. Life expectancy of 12 weeks or more.
7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status
(PS) of 0 to 2.
8. 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.
9. 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:
1. 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.
2. Inadequate renal function defined as creatinine >1.5 × ULN or calculated creatinine
clearance < 40 mL/min.
3. Absolute neutrophil count (ANC) < 1.0×109/L, or Platelets < 30×109/L, or Hemoglobin
< 8.5 g/dL.
4. International Normalized Ratio (INR) > 2.3.
5. Subjects with a history of liver transplantation.
6. Subjects with poorly controlled hypertension, diabetes or other serious heart or
lung diseases, or with serious dysfunction.
7. Subjects with extrahepatic metastasis who had not received first-line systemic
therapies (excluding those who are not eligible for systemic therapies) or who were
receiving effective systemic therapy currently.
8. Subjects who had prior anticancer treatment with any locoregional therapies,
antiangiogenic targeted therapies, immune checkpoint inhibitors or chemotherapy
(within 4 weeks, or within 2 weeks in case of sorafenib), radiotherapy (within 3
weeks), or active traditional Chinese medicine (within 2 weeks) before the first
dose of study treatment, except for the treatments after which the disease still
progressed according to mRECIST.
9. 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).
10. Subjects with 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.
11. Uncontrolled active infection (eg, lung infections, or abdominal infections).
12. 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.
13. HBV DNA greater than 500 copies/mL, or HCV RNA greater than 15 U/mL.
14. Subject is positive for Human Immunodeficiency Virus (HIV).
15. Any subject who is allergic to MRI contrast agents.
16. Pregnant/lactating women, or women who have the possibility of pregnancy.
17. Participation in other investigational drug trials within 4 weeks prior to
initiation of this study treatment.
18. Any medical or other condition which, in the opinion of the investigator, would
preclude participation in this clinical trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
September 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Shanghai Changzheng Hospital
Agency class:
Other
Source:
Shanghai Changzheng Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06418659
