Trial Title:
Chidamide + Regorafenib in Hepatocellular Carcinoma (HCC)
NCT ID:
NCT05770882
Condition:
Hepatocellular Carcinoma (HCC)
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Conditions: Keywords:
HCC
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Chidamide
Description:
Subjects will receive a single dose of chidamide. 5mg tablet. One dose every three days.
Arm group label:
Part I safety; and Part II cohort expansion
Other name:
Tucidinostat
Other name:
HBI-8000
Intervention type:
Drug
Intervention name:
Regorafenib
Description:
Subjects will receive a single dose of Regorafenib. 40mg tablet. One dose daily.
Arm group label:
Part I safety; and Part II cohort expansion
Other name:
Stivarga
Other name:
BAY 73-4506
Summary:
This open-label, phase Ib/II, multicenter study evaluated the safety, tolerability,
efficacy, and PK of chidamide in combination with regorafenib in patients with HCC.
Chidamide, a histone deacetylase inhibitor, functions as a tumor inhibitor. Regorafenib,
a receptor tyrosine kinase inhibitor, was approved as second-line systemic treatment for
HCC patients.
Detailed description:
This is an open-label, multicenter, phase Ib/II study, which includes a Part I (phase Ib)
and a Cohort Expansion part (Part II; phase II). Part I of the study is designed to
assess the safety, tolerability, PK profiles, efficacy, and PD biomarkers of the study
medications in patients with HCC. Part II of the study is designed to assess the
efficacy, safety, and PD biomarkers.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histological or cytological confirmation of HCC or non-invasive diagnosis of HCC as
per American Association for the Study of Liver Diseases (AASLD) criteria in
patients with a confirmed diagnosis of cirrhosis.
2. Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC that cannot benefit from
treatments of established efficacy with higher priority such as resection, local
ablation, chemoembolization or first-line systemic therapy.
3. Has received and failed one front-line systemic treatment with either sorafenib,
lenvatinib, or combination of PD-1/PD-L1 immune checkpoint inhibitor (ICI;
anti-PD-1/PD-L1 mAb) plus bevacizumab, lenvatinib or anti-CTLA-4 mAb.
4. Tolerability of prior treatment with sorafenib or lenvatinib. Tolerability to
previous sorafenib treatment is defined as not less than 20 days at a minimum daily
dose of 400 mg QD within the last 28 days prior to withdrawal. Tolerability to
previous lenvatinib treatment is defined as not less than 20 days at a daily dose of
8 mg QD for patients ≥60 kg or 4 mg QD for patients <60 kg days within the last 28
days prior to withdrawal.
5. Liver function status Child-Pugh Class A. Child-Pugh status should be calculated
based on clinical findings and laboratory results during the screening period.
6. Local or loco-regional therapy of intrahepatic tumor lesions (e.g., surgery,
radiation therapy, hepatic arterial embolization or infusion chemotherapy,
chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or
cryoablation) must have been completed ≥4 weeks before the first dose of study
medication.
7. ECOG PS of 0 or 1.
8. With adequate bone marrow, liver, and renal functions, as assessed by the following
laboratory tests conducted within 7 days before the first dose of study medication:
9. At least one uni-dimensional measurable lesion by computed tomography scan or
magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1 and modified RECIST for HCC (mRECIST). Tumor lesions situated in a
previously irradiated area, or in an area subjected to other loco-regional therapy,
may be considered measurable if there has been demonstrated progression in the
lesion.
10. With a life expectancy of at least 3 months.
11. Females of childbearing potential and males must agree to use adequate contraception
since signing of the informed consent form until at least 2 months after the last
study drug administration.
12. Female patients of childbearing potential must have a negative urine or serum
pregnancy test.
13. Able to take oral medication.
14. Has ability to understand and the willingness to provide a written informed consent
document.
Exclusion Criteria:
1. With history of organ transplantation or candidates for liver transplantation.
2. Prior treatment with regorafenib.
3. First-line treatment within 4 weeks before the first dose of study medication.
4. Permanent discontinuation of prior sorafenib or lenvatinib therapy due to
drug-related toxicity.
5. Known history or symptomatic metastatic brain or meningeal tumors. Note: If patients
showed symptomatic brain metastases at screening, magnetic resonance imaging (MRI)
or computed tomography (CT) scanning should be performed to demonstrate any current
evidence of progressive brain metastases.
6. Major surgical procedure or significant traumatic injury within 28 days before the
first dose of study medication.
7. With uncontrolled or significant cardiovascular diseases
8. With the size of fluid area detected by cardiac ultrasonography in cavum pericardium
≥ 10 mm.
9. Patients with pheochromocytoma.
10. Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis
treatment).
11. Pleural effusion or ascites that causes respiratory compromise (National Cancer
Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 grade ≥2
dyspnea).
12. Ongoing infection grade >2 according to NCI-CTCAE v5.0. Hepatitis B is allowed if no
active replication is present. Hepatitis C is allowed if no antiviral treatment is
required.
13. Clinically significant bleeding NCI-CTCAE v5.0 grade ≥3 within 30 days before the
first dose of study medication.
14. Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism
within 6 months before the first dose of study medication..
15. With autoimmune disorders or history of organ transplantation who require
immunosuppressive therapy
16. Non-healing wound, ulcer, or bone fracture.
17. Renal failure requiring hemo- or peritoneal dialysis.
18. Interstitial lung disease with ongoing signs and symptoms at the time of screening.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Chang Gung Memorial Hospital, Kaohsiung
Address:
City:
Kaohsiung
Country:
Taiwan
Status:
Recruiting
Investigator:
Last name:
Sheng-Nan Lu
Email:
Principal Investigator
Facility:
Name:
China Medical University Hospital
Address:
City:
Taichung
Country:
Taiwan
Status:
Recruiting
Investigator:
Last name:
Hsueh-Chou Lai
Email:
Principal Investigator
Facility:
Name:
National Cheng Kung University Hospital
Address:
City:
Tainan
Country:
Taiwan
Status:
Recruiting
Investigator:
Last name:
Pin-Nan Cheng
Email:
Principal Investigator
Facility:
Name:
Taipei Veterans General Hospital
Address:
City:
Taipei
Country:
Taiwan
Status:
Recruiting
Investigator:
Last name:
Yi-Hsiang Huang
Email:
Principal Investigator
Facility:
Name:
Chang Gung Memorial Hospital, Linkou
Address:
City:
Taoyuan
Country:
Taiwan
Status:
Recruiting
Investigator:
Last name:
Chen-Chun Lin
Email:
Principal Investigator
Start date:
April 25, 2023
Completion date:
January 31, 2026
Lead sponsor:
Agency:
Great Novel Therapeutics Biotech & Medicals Corporation
Agency class:
Industry
Source:
Great Novel Therapeutics Biotech & Medicals Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05770882
