Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

Regorafenib and Yttrium-90 Radioembolization for Treatment of Unresectable Hepatocellular Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Unresectable Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Regorafenib; Radiation: TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Benjamin Spieler, MD; Phone Number: (305) 243-4229; Email: bspieler@med.miami.edu
• Study Contact Backup: Name: Lynn G Feun, MD; Phone Number: (305) 243-4981; Email: lfeun@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Principal Investigator: Benjamin Spieler, MD
      • Contact: Benjamin Spieler, MD; Phone Number: (305) 243-4229; Email: bspieler@med.miami.edu
      • Contact: Lynn G Feun, MD; Phone Number: (305) 243-4981; Email: lfeun@med.miami.edu
      • Principal Investigator: Lynn G Feun, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients ages 18 years old and above.
2. Unresectable Hepatocellular Carcinoma (HCC).
3. Child-Pugh A-B7.
4. Serum bilirubin < 1.5 upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN.
5. Serum creatinine ≤ 1.5 x ULN.
6. 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.
7. Platelet count > 100,000 platelets/mm3, hemoglobin (Hb) 9 g/dL, and absolute neutrophil count (ANC) 1,500 neutrophils/mm3.
8. Mapping angiogram procedure shows radioembolization is feasible and safe to perform.
9. No prior systemic therapy for HCC.
10. Participant agrees to comply with the contraception requirements as described in protocol.

Exclusion Criteria:

1. Angiogram shows vascular shunting which prevents radioembolization.
2. Prior radioembolization.
3. Major extrahepatic disease.
4. Participants with brain metastases.
5. Participants who have not recovered from major surgery. Participants must not undergo any major surgery at or within 30 days prior to study enrollment.
6. Presence of a non-healing wound, non-healing ulcer, or bone fracture.
7. Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
8. Ongoing infection > Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
9. Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI CTCAE v5.0] on repeated measurement) despite optimal medical management.

10. Active or clinically significant cardiac disease including:

    1. Congestive heart failure - New York Heart Association (NYHA) > Class II.
    2. Active coronary artery disease.
    3. Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
    4. Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before study enrollment, or myocardial infarction within 6 months before study enrollment.
11. Evidence or history of bleeding diathesis or coagulopathy.
12. Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
13. Participants with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment or within 6 months of informed consent.
14. Participants with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated ductal carcinoma in situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive aerodigestive neoplasms, or superficial bladder tumor. Participants surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed. All cancer treatments must be completed at least 3 years prior to registration.
15. Participants with impaired decision-making capacity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Regorafenib in combination with Radioembolization Group; 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; 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.; Other Names: Stivarga; Radiation: TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization; 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.; Other Names: Y-90 TARE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is the proportion of patients achieving complete response (CR) or partial response (PR) as the best response. Response will be assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for hepatocellular carcinoma.	Up to 36 months
Time to Tumor Progression	Time-to-tumor progression is defined as the period of time in months from start date of study treatment until documented date of confirmed disease progression. For participants without progression, follow-up time will be censored at the date of last disease assessment (as per mRECIST).	Up to 36 months
Duration of Overall Response (DOR)	The duration of overall response (DOR) is measured in months from the time measurement criteria are met for complete response (CR) or partial response (PR) per mRECIST criteria, until the first date that recurrent or progressive disease is documented. For participants without progression, follow-up time will be censored at the date of last disease assessment, per mRECIST criteria.	Up to 36 months
Progression-Free Survival (PFS)	Progression-free survival (PFS) is defined as the elapsed time in months from the first date of study treatment until documented disease progression, per mRECIST criteria or death from any cause, whichever is earlier. For participants who remain alive without progression, follow-up time will be censored at the date of last disease assessment, per mRECIST criteria.	Up to 36 months
Overall Survival (OS)	Overall survival (OS) is defined as the elapsed time in months from date of first study treatment until death from any cause. Participants without documented death will be censored at the last date known to be alive.	Up to 36 months

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: Bayer
• Investigators: Principal Investigator: Lynn G Feun, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; regorafenib
• Other Study ID Numbers: 20230806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No