Status:
ACTIVE_NOT_RECRUITING
Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7
Lead Sponsor:
Translational Research in Oncology
Collaborating Sponsors:
Bayer
Conditions:
Carcinoma, Hepatocellular
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and pembrolizumab (Rego-Pembro) versus transarterial chemoembolization (TACE) or tr...
Detailed Description
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of systemic therapy with Rego-Pembro versus loco-regional therapy with TACE or TARE, for the first...
Eligibility Criteria
Inclusion
- Signed and dated Patient Informed Consent Form (PICF)
- ≥ 18 years-old at the time of PICF signature
- Confirmed diagnosis of HCC
- 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
- Beyond up-to-seven criteria
- Disease amenable to TACE or TARE and no contradiction to intra-arterial treatment
- Measurable disease by CT or MRI as per RECIST 1.1
- No prior systemic therapy or loco-regional therapy for HCC
- Adequate hematologic and organ function
- Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures
- Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test
- Use of highly-effective contraceptive methods in women of CBP and men
- Patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection are eligible if they meet criteria as defined within the protocol
Exclusion
- No measurable tumor of a diffuse infiltrative HCC type.
- Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes.
- Clinically meaningful ascites.
- 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.
- Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.
- 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.
- Requirement of systemic treatment with either corticosteroids or other immunosuppressive medications ≤ 14 days prior to randomization.
- Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, or clinically significant acute lung diseases.
- Cardiovascular conditions as defined within the protocol.
- Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed ≤ 2 years before randomization.
- Persistent proteinuria of NCI-CTCAE v5.0 Grade 3.
- Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Key Trial Info
Start Date :
October 11 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
February 28 2026
Estimated Enrollment :
496 Patients enrolled
Trial Details
Trial ID
NCT04777851
Start Date
October 11 2023
End Date
February 28 2026
Last Update
May 15 2025
Active Locations (26)
Enter a location and click search to find clinical trials sorted by distance.
1
UCLA Santa Monica Hematology Oncology
Santa Monica, California, United States, 90404
2
UCL SAINT LUC - UC Louvain
Brussels, Belgium, 1200
3
Antwerp University Hospital
Edegem, Belgium, 2650
4
CHU Amiens-Picardie
Amiens, France, 80054