Chidamide + Regorafenib in Hepatocellular Carcinoma (HCC)

Last updated: March 7, 2025
Sponsor: Great Novel Therapeutics Biotech & Medicals Corporation
Overall Status: Terminated

Phase

1/2

Condition

Carcinoma

Treatment

Chidamide

Regorafenib

Clinical Study ID

NCT05770882
KEPIDA-1
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Histological or cytological confirmation of HCC or non-invasive diagnosis of HCC asper American Association for the Study of Liver Diseases (AASLD) criteria inpatients with a confirmed diagnosis of cirrhosis.

  2. Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC that cannot benefit fromtreatments of established efficacy with higher priority such as resection, localablation, 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 toprevious sorafenib treatment is defined as not less than 20 days at a minimum dailydose of 400 mg QD within the last 28 days prior to withdrawal. Tolerability toprevious 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 28days prior to withdrawal.

  5. Liver function status Child-Pugh Class A. Child-Pugh status should be calculatedbased 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, orcryoablation) must have been completed ≥4 weeks before the first dose of studymedication.

  7. ECOG PS of 0 or 1.

  8. With adequate bone marrow, liver, and renal functions, as assessed by the followinglaboratory tests conducted within 7 days before the first dose of study medication:

  9. At least one uni-dimensional measurable lesion by computed tomography scan ormagnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST for HCC (mRECIST). Tumor lesions situated in apreviously irradiated area, or in an area subjected to other loco-regional therapy,may be considered measurable if there has been demonstrated progression in thelesion.

  10. With a life expectancy of at least 3 months.

  11. Females of childbearing potential and males must agree to use adequate contraceptionsince signing of the informed consent form until at least 2 months after the laststudy drug administration.

  12. Female patients of childbearing potential must have a negative urine or serumpregnancy test.

  13. Able to take oral medication.

  14. Has ability to understand and the willingness to provide a written informed consentdocument.

Exclusion

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 todrug-related toxicity.

  5. Known history or symptomatic metastatic brain or meningeal tumors. Note: If patientsshowed symptomatic brain metastases at screening, magnetic resonance imaging (MRI)or computed tomography (CT) scanning should be performed to demonstrate any currentevidence of progressive brain metastases.

  6. Major surgical procedure or significant traumatic injury within 28 days before thefirst 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 paracentesistreatment).

  11. Pleural effusion or ascites that causes respiratory compromise (National CancerInstitute - Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 grade ≥2dyspnea).

  12. Ongoing infection grade >2 according to NCI-CTCAE v5.0. Hepatitis B is allowed if noactive replication is present. Hepatitis C is allowed if no antiviral treatment isrequired.

  13. Clinically significant bleeding NCI-CTCAE v5.0 grade ≥3 within 30 days before thefirst 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 embolismwithin 6 months before the first dose of study medication..

  15. With autoimmune disorders or history of organ transplantation who requireimmunosuppressive 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.

Study Design

Total Participants: 7
Treatment Group(s): 2
Primary Treatment: Chidamide
Phase: 1/2
Study Start date:
April 25, 2023
Estimated Completion Date:
January 17, 2025

Study 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.

Connect with a study center

  • Chang Gung Memorial Hospital, Kaohsiung

    Kaohsiung,
    Taiwan

    Site Not Available

  • China Medical University Hospital

    Taichung,
    Taiwan

    Site Not Available

  • National Cheng Kung University Hospital

    Tainan,
    Taiwan

    Site Not Available

  • Taipei Veterans General Hospital

    Taipei,
    Taiwan

    Site Not Available

  • Chang Gung Memorial Hospital, Linkou

    Taoyuan,
    Taiwan

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.