- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05770882
Chidamide + Regorafenib in Hepatocellular Carcinoma (HCC)
February 22, 2024 updated by: Great Novel Therapeutics Biotech & Medicals Corporation
A Phase Ib/II, Two-part, Non-randomized, Open-label Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Chidamide in Combination With Regorafenib in Patients With Hepatocellular Carcinoma
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
46
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Chia-Nan Chen, Ph.D.
- Phone Number: +886-2-2785-1399
- Email: alex.chen@gntbm.com.tw
Study Locations
-
-
-
Kaohsiung, Taiwan
- Recruiting
- Chang Gung Memorial Hospital, Kaohsiung
-
Principal Investigator:
- Sheng-Nan Lu
-
Taichung, Taiwan
- Recruiting
- China Medical University Hospital
-
Principal Investigator:
- Hsueh-Chou Lai
-
Tainan, Taiwan
- Recruiting
- National Cheng Kung University Hospital
-
Principal Investigator:
- Pin-Nan Cheng
-
Taipei, Taiwan
- Recruiting
- Taipei Veterans General Hospital
-
Principal Investigator:
- Yi-Hsiang Huang
-
Taoyuan, Taiwan
- Recruiting
- Chang Gung Memorial Hospital, Linkou
-
Principal Investigator:
- Chen-Chun Lin
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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.
- 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.
- 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.
- 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.
- Liver function status Child-Pugh Class A. Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
- 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.
- ECOG PS of 0 or 1.
- 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:
- 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.
- With a life expectancy of at least 3 months.
- 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.
- Female patients of childbearing potential must have a negative urine or serum pregnancy test.
- Able to take oral medication.
- Has ability to understand and the willingness to provide a written informed consent document.
Exclusion Criteria:
- With history of organ transplantation or candidates for liver transplantation.
- Prior treatment with regorafenib.
- First-line treatment within 4 weeks before the first dose of study medication.
- Permanent discontinuation of prior sorafenib or lenvatinib therapy due to drug-related toxicity.
- 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.
- Major surgical procedure or significant traumatic injury within 28 days before the first dose of study medication.
- With uncontrolled or significant cardiovascular diseases
- With the size of fluid area detected by cardiac ultrasonography in cavum pericardium ≥ 10 mm.
- Patients with pheochromocytoma.
- Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
- Pleural effusion or ascites that causes respiratory compromise (National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 grade ≥2 dyspnea).
- 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.
- Clinically significant bleeding NCI-CTCAE v5.0 grade ≥3 within 30 days before the first dose of study medication.
- 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..
- With autoimmune disorders or history of organ transplantation who require immunosuppressive therapy
- Non-healing wound, ulcer, or bone fracture.
- Renal failure requiring hemo- or peritoneal dialysis.
- Interstitial lung disease with ongoing signs and symptoms at the time of screening.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part I safety; and Part II cohort expansion
Part I: The safety of drug combination will be studied. Part II: The drug combination will be further evaluated in the cohort expansion phase. |
Subjects will receive a single dose of chidamide.
5mg tablet.
One dose every three days.
Other Names:
Subjects will receive a single dose of Regorafenib.
40mg tablet.
One dose daily.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse event (AE)
Time Frame: From the first day of treatment until progressive disease or death, assessed up to 12 months
|
To analyze the frequency, percentage of patients with study medications of adverse events
|
From the first day of treatment until progressive disease or death, assessed up to 12 months
|
Maximum tolerated dose(MTD) / maximum feasible dose (MFD)
Time Frame: From start of treatment Cycle1 Day1 until completion of one cycle of treatment (maximum 28 days)
|
To assess tolerability/feasible of study medications dose
|
From start of treatment Cycle1 Day1 until completion of one cycle of treatment (maximum 28 days)
|
Pharmacokinetics profiles - (AUC0-t)
Time Frame: Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Area under the plasma concentration-time curve from time zero to time t(AUC0-t)
|
Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Pharmacokinetics profiles - (AUC0-∞)
Time Frame: Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Area under the plasma concentration-time curve from time zero to infinity(AUC0-∞)
|
Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Pharmacokinetics profiles - (Cmax)
Time Frame: Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Maximum plasma concentration(Cmax)
|
Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Pharmacokinetics profiles - (Tmax)
Time Frame: Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Time to maximum plasma concentration(Tmax)
|
Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Pharmacokinetics profiles - (T1/2)
Time Frame: Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Half-life(T1/2)
|
Blood samples collected on Days 1-4 and 18-21 of Cycle 1, pre-dose and up to 72 hours post-dose (28 days/cycle)
|
Objective response rate (ORR)
Time Frame: Objective Response Rate is assessed every 8 weeks from start of treatment until progressive disease is documented (approximately 6 months)
|
The percentage of patients with CR and PR of total number of analysis set
|
Objective Response Rate is assessed every 8 weeks from start of treatment until progressive disease is documented (approximately 6 months)
|
Progression-free survival (PFS)
Time Frame: From the first day of treatment until disease progression or death from any cause, assessed up to 12 months
|
The time from first day of dosing until the date of first objective disease progression or death
|
From the first day of treatment until disease progression or death from any cause, assessed up to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: 1 year
|
The time from the first day of dosing until the date of death
|
1 year
|
Time to progression (TTP)
Time Frame: 1 year
|
The time from the first day of dosing until the date of progression
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Chia-Nan Chen, Ph.D., Great Novel Therapeutics Biotech & Medicals Corporation
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 25, 2023
Primary Completion (Estimated)
January 31, 2025
Study Completion (Estimated)
January 31, 2026
Study Registration Dates
First Submitted
February 7, 2023
First Submitted That Met QC Criteria
March 14, 2023
First Posted (Actual)
March 16, 2023
Study Record Updates
Last Update Posted (Actual)
February 23, 2024
Last Update Submitted That Met QC Criteria
February 22, 2024
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- KEPIDA-1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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