Regorafenib-pembrolizumab vs. TACE/TARE in intermediatestage HCC beyond up-to-7 (REPLACE)

JRCT ID: jRCT2051240126

Registered date:18/09/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Intermediate-stage hepatocellular carcinoma with beyond up-to-7 criteria
• Date of first enrollment: 30/09/2024
• Target sample size: 50
• Countries of recruitment: France,Japan,Belgium,Japan,Germany,Japan,Italy,Japan,Spain,Japan,US,Japan,Georgia,Japan,Serbia,Japan,Turkey,Japan,South Korea,Japan,Taiwan,Japan,Hong Kong,Japan,Romania,Japan
• Study type: Interventional

Intervention(s)

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 a 6-week cycle.

Control arm: Patients will be treated with TACE "on-demand" according to site's standard.

Outcome(s)

• Primary Outcome: Progression-free Survival (PFS) Assessed by the Investigator using mRECIST

Secondary Outcome

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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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.

Related Information

• Primary Sponsor: Kudo Masatoshi
• Source(s) of Monetary Support: Bayer AG
• Secondary ID(s): NCT04777851,2022-501969-42-00