Regorafenib and Nivolumab Combined Versus TACE in Intermediate-Stage HCC Beyond Up-to-7 (RENOTACE)

• Status: Not yet recruiting
• Trial end date: 2025-05-15
• Target enrollment: 0
• Participant gender: All

Summary

RENOTACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and nivolumab (Rego-Nivo) versus transarterial chemoembolization (TACE) 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 nivolumab (rego-nivo)

• Control arm: Transarterial chemoembolization (TACE)

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.

It is hypothesized that combining regorafenib and nivolumab, may be advantageous over standard treatment at an earlier HCC stage such as the intermediate-stage. This drug combination was tested previously in pre-treated metastatic gastric and colorectal cancer (Phase 1b, REGONIVO trial). The 80 mg regorafenib dose had a manageable safety profile and encouraging antitumor activity (objective tumor response 40 precent) in patients with heavily pretreated disease. Based on these promising results, the Rego-Nivo combination is being tested in a number of ongoing clinical trials.

RENOTACE will compare the efficacy and safety of the standard of care approach in patients with this stage (i.e. TACE) versus Rego-Nivo, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Although there are a number of trials comparing TACE with TACE in combination with systemic therapy, this will be the first trial comparing TACE with systemic therapy alone, an approach that could potentially represent a shift in the management of intermediate-stage HCC.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Translational Research in Oncology
• Collaborator: Bayer
• Treatments: Nivolumab

Criteria

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 EH/MVI

• 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

• Measurable disease as per RECIST 1.1

• No prior 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

Exclusion Criteria:

• No measurable tumor of a diffuse infiltrative HCC type

• Fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes

• Clinically meaningful ascites

• Prior treatment with regorafenib or a checkpoint inhibitor or other form of immunotherapy

• Concurrent participation in another interventional clinical trial

• 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 (>10 mg daily prednisone equivalents) or other immunosuppressive medications

• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

• Clinically-significant uncontrolled cardiovascular conditions.

• Infection > Grade 2 NCI-CTCAE v5.0

• Evidence or history of bleeding diasthesis or any hemorrhage or bleeding event

• Non-healing wound, ulcer, or bone fracture

• Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization

• Patient has known history of human immunodeficiency virus infection

• Persistent proteinuria of NCI-CTCAE v5.0 Grade 3

• Known HIV infection

• Unresolved clinically-significant toxicity greater than NCI-CTCAE v5.0 Grade 1

• Patient has any other concurrent severe and/or uncontrolled medical condition, social situation, etc. that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol

• Pregnant or breast-feeding