Intermediate-stage hepatocellular carcinoma with beyond up-to-7 criteria
Conditions
Interventions
Investigational arm: Regorafenib at a dose of 90 mg orally once daily on days 1 to 21 of a 4-week cycle. In combination with Pembrolizumab 400 mg using a 30-minutes intravenously infusion, on day 1 of
Sponsors
Kudo Masatoshi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Signed and dated Patient Informed Consent Form (PICF) 2 >= 18 years-old at the time of PICF signature 3 Confirmed diagnosis of HCC 4 Intermediate-stage HCC, defined as follows: - Multinodular HCC localized to the liver - No evidence of MVI or EHS - Not amenable to curative treatment - Child-Pugh Class A - ECOG PS 0 or 1 - ALBI grade 1 or 2 5 Beyond up-to-seven criteria 6 Disease amenable to TACE or TARE and no contradiction to intra-arterial treatment 7 Measurable disease by CT or MRI as per RECIST 1.1 8 No prior systemic therapy or loco-regional therapy for HCC 9 Adequate hematologic and organ function 10 Patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection are eligible if they meet criteria as defined within the protocol 11 Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures 12 Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test 13 Use of highly-effective contraceptive methods in women of CBP and men
Exclusion criteria
Exclusion criteria: 1. No measurable tumor of a diffuse infiltrative HCC type. 2. Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes. 3. Clinically meaningful ascites. 4. Prior treatment with regorafenib, a PD-1, PD-L1/PD-L2, or cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 5. Major surgical procedure, open biopsy, or significant traumatic injury <=28 days prior to randomization. 6. Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. 7. Requirement of systemic treatment with either corticosteroids or other immunosuppressive medications <= 14 days prior to randomization. 8. Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, or clinically significant acute lung diseases. 9. Cardiovascular conditions as defined within the protocol. 10. Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed <= 2 years before randomization. 11. Persistent proteinuria of NCI-CTCAE v5.0 Grade 3. 12. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival (PFS) Assessed by the Investigator using mRECIST | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PFS assessed by the Investigator using RECIST 1.1 2. PFS assessed by Blinded Independent Central Review (BICR) using mRECIST and RECIST 1.1 3. Overall Survival (OS) 4. Overall Response Rate (ORR) assessed by Investigator and BICR as per mRECIST and RECIST 1.1 5. Time to unTACEable Progression (TTUP) 6. Duration of Response (DOR) 7. Frequency and severity of AEs and laboratory abnormalities. 8. Change from baseline in the physical functioning sub-scale score and global health status/QoL scale score as assessed by EORTC QLQ-C30, EORTC QLQ-HCC18 and EQ-5D-5L. | — |
Countries
Belgium, France, Georgia, Germany, Hong Kong, Italy, Japan, Romania, Serbia, South Korea, Spain, Taiwan, Turkey, US
Contacts
Public ContactClinical Trial Coordination Office
ClinChoice K.K.
Outcome results
None listed