Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

NCT06902246 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 20230806
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effects that Regorafenib in combination with Yttrium-90 (Y-90) radioembolization has on patients with unresectable hepatocellular carcinoma.

Conditions

Unresectable Hepatocellular Carcinoma; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Disease Control Rate (DCR) Measured by Number of Participants

  Disease Control Rate (DCR) is defined as the number of participants experiencing a best response of complete response (CR), partial response (PR), or stable disease (SD) after receiving protocol therapy. Response will be assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for hepatocellular carcinoma.

  Up to 24 months

• Number of Participants Experiencing Treatment Related Adverse Events

  The number of participants experiencing treatment-related adverse events (AEs) in participants receiving protocol therapy will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

  Up to 25 months

• Number of Participants Experiencing Treatment Related Serious Adverse Events

  The number of participants experiencing treatment-related serious adverse events (SAEs) in participants receiving protocol therapy will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

  Up to 25 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to 36 months

• Time to Tumor Progression

  Up to 36 months

• Duration of Overall Response (DOR)

  Up to 36 months

• Progression-Free Survival (PFS)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (1)

Regorafenib in combination with Radioembolization Group

EXPERIMENTAL

Participants in this group will receive combination therapy of Regorafenib and Yttrium 90 Trans-Arterial Radioembolization (Y90 TARE). Participants will receive therapy until unacceptable toxicity, disease progression, or withdrawal of consent, whichever occurs first. Total participation duration is approximately 37 months.

Drug: Regorafenib; Radiation: TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization

Interventions

Regorafenib DRUG

Participants will orally self-administer Regorafenib tablets for the first 21 days of each 28-day cycle as follows. Dose-escalation will occur only if there are no significant drug-related adverse events: * Safety Run-in Phase: For the first six (6) participants enrolled. The starting dose is 80 mg/day during Cycles 1 and 2. In Cycle 3, the starting dose is 80 mg/day on Days 1 to 7, escalating to 120 mg/day on Days 8 to 14, and then escalating to a maximum dose of 160 mg/day on Days 15 to 21. Participants will continue to receive the maximum tolerated dose determined at the end of Cycle 3. * Phase 2: For participants enrolled after the Safety Run-in phase. In Cycle 1, the starting dose is 80 mg/day on Days 1 to 7, escalating to 120 mg/day on Days 8 to 14, and then escalating to a maximum dose 160 mg/day on Days 15 to 21. From Cycle 2 onward, participants will take 160 mg/day (or maximum tolerated dose from Cycle 1), on Days 1 to 21.

Also known as: Stivarga

Regorafenib in combination with Radioembolization Group

TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization RADIATION

Y-90 absorbed glass microspheres will be administered standard of care once via the percutaneous trans-arterial approach after the first 3 weeks of Regorafenib treatment but before Day 28. Additional Y-90 absorbed glass microsphere administration is allowed for treatment of baseline disease in the absence of disease progression within 6 months of the initial Y-90 TARE treatment.

Also known as: Y-90 TARE

Regorafenib in combination with Radioembolization Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ages 18 years old and above.
• Unresectable Hepatocellular Carcinoma (HCC).
• Child-Pugh A-B7.
• Serum bilirubin \< 1.5 upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN.
• Serum creatinine ≤ 1.5 x ULN.
• International normalized ratio (INR)/Partial thromboplastin time (PTT) ≤ 1.5 x ULN. Note: Participants who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists.
• Platelet count \> 100,000 platelets/mm3, hemoglobin (Hb) 9 g/dL, and absolute neutrophil count (ANC) 1,500 neutrophils/mm3.
• Mapping angiogram procedure shows radioembolization is feasible and safe to perform.
• No prior systemic therapy for HCC.
• Participant agrees to comply with the contraception requirements as described in protocol.

You may not qualify if:

• Angiogram shows vascular shunting which prevents radioembolization.
• Prior radioembolization.
• Major extrahepatic disease.
• Participants with brain metastases.
• Participants who have not recovered from major surgery. Participants must not undergo any major surgery at or within 30 days prior to study enrollment.
• Presence of a non-healing wound, non-healing ulcer, or bone fracture.
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
• Ongoing infection \> Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
• Uncontrolled hypertension (systolic pressure \> 140 mm Hg or diastolic pressure \> 90 mm Hg \[NCI CTCAE v5.0\] on repeated measurement) despite optimal medical management.
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) \> Class II.
• Active coronary artery disease.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before study enrollment, or myocardial infarction within 6 months before study enrollment.
• Evidence or history of bleeding diathesis or coagulopathy.

Sponsors & Collaborators

• University of Miami: lead
• Bayer: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Lynn G Feun, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lynn G Feun, MD

CONTACT

(305) 243-4981; lfeun@med.miami.edu

Benjamin Spieler, MD

CONTACT

(305) 243-4229; bspieler@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2031
• Last Updated: May 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)