Ignite Creation Date:
2025-12-24 @ 11:38 PM
Ignite Modification Date:
2026-01-01 @ 1:39 AM
Study NCT ID:
NCT04777851
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-05-15
First Post:
2021-02-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7
Sponsor:
Translational Research in Oncology
Organization:
Study Overview
Official Title:
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:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
REPLACE
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 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.
* 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| EU CT # 2022-501969-42-00 | OTHER | European Medicines Agency (EMA) | View |