NCT04777851

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

A Phase III, Multicenter, Randomized, Open-label Trial to Evaluate the Safety and Efficacy of Systemic Therapy With Regorafenib and Pembrolizumab Versus Locoregional Therapy With Transarterial Chemoembolization or Transarterial Radioembolization, for the First-line Treatment of Intermediate-stage Hepatocellular Carcinoma With Beyond Up-to-7 Criteria

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Translational Research in Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Approximately 496 patients (\~248 in each arm) from approximately 80 sites will be randomized in order to power the trial efficiently to measure a clinically meaningful improvement for the primary endpoint, PFS according to mRECIST based on the Investigator´s assessment. The trial will include patients who have been diagnosed with intermediate-stage HCC by biopsy, cytology or diagnostic imaging, such as dynamic computed tomography (CT) or magnetic resonance imaging (MRI), according to the criteria of the American Association for the Study of Liver Diseases (AASLD). Patients should have at least one measurable lesion per RECIST 1.1, disease not amenable to curative treatment but amenable to loco-regional therapy with TACE (cTACE or DEB-TACE) or TARE, ECOG PS 0-1, Child-Pugh class A, and beyond up-to-7 criteria. The trial will include the following phases: * Screening * Treatment * Follow-up Randomized patients will receive either: Investigational arm (Arm A): -Regorafenib at a dose of 90 mg orally q.d. on days 1 to 21 of a 4-week cycle. In combination with: -Pembrolizumab 400 mg using a 30-minutes i.v. infusion, on day 1 (D1) of a 6-week cycle. Control arm (Arm B): -Patients will be treated with TACE or TARE "on-demand" according to site's standard, with the goal of controlling all known liver lesions. In both arms, patients will receive trial treatment (Rego-Pembro or TACE/TARE) until PD per mRECIST, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria are met.

Conditions

• Carcinoma, Hepatocellular

Interventions

Type	Name	Description
DRUG	Regorafenib in combination with pembrolizumab	Randomized patients will receive regorafenib at a dose of 90 mg per day by mouth on days 1 to 21 of a 28-day cycle, in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 (D1) of a 6-week cycle.
PROCEDURE	Loco-regional therapy	Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice.

Timeline

• Start date: 2023-10-11
• Primary completion: 2026-02-26
• Completion: 2026-02-26
• First posted: 2021-03-02
• Last updated: 2026-03-09

Locations

26 sites across 13 countries: United States, Belgium, France, Georgia, Germany, Hong Kong, Italy, Romania, Serbia, South Korea, Spain, Taiwan, Turkey (Türkiye)

Regulatory

• FDA-regulated drug study