TerminatedPhase 3

Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7

Stopped: The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.

United States, Belgium, France45 participantsStarted 2023-10-11

Plain-language 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 transarterial radioembolization (TARE) for the first-line treatment of hepatocellular carcinoma (HCC or liver cancer). Approximately 496 patients in around 80 clinical sites worldwide will be randomized to receive either: * Investigational arm: Regorafenib in combination with pembrolizumab * Control arm: Transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) In both arms, patients will receive trial treatment until progressive disease, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria is met. After trial treatment discontinuation, subsequent treatment will be administered according to the Investigator's clinical judgment.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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 Criteria: * 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 …

What they're measuring

Progression-free Survival (PFS) Assessed by the Investigator as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC

Timeframe: up to 3.5 years

Trial details

NCT IDNCT04777851

SponsorTranslational Research in Oncology

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-02-26

View on ClinicalTrials.gov More Carcinoma, Hepatocellular trials