Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

NCT ID: NCT06902246

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-05
• Study Completion Date: 2031-01-05

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Regorafenib

Intervention Type: 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.

TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Other Intervention Names

Stivarga; Y-90 TARE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Lynn Feun, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lynn G Feun, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Lynn G Feun, MD

Role: CONTACT

lfeun@med.miami.edu

(305) 243-4981

Benjamin Spieler, MD

Role: CONTACT

bspieler@med.miami.edu

(305) 243-4229

Facility Contacts

Lynn G Feun, MD

Role: primary

lfeun@med.miami.edu

(305) 243-4981

Benjamin Spieler, MD

Role: backup

bspieler@med.miami.edu

(305) 243-4229

Other Identifiers

20230806

Identifier Type: -

Identifier Source: org_study_id