Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

Phase 2

Not yet recruiting

• Conditions: Unresectable Hepatocellular Carcinoma; Hepatocellular Carcinoma
• Interventions: Drug: Regorafenib; Radiation: TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization

• Registration Number: NCT06902246
• Lead Sponsor: University of Miami

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-24
• Study First Submitted QC: 2025-03-24
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-30
• Last Update Posted: 2025-03-30
• Study Start: 2025-06-01
• Primary Completion: 2030-06-01
• Study Completion: 2030-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 28

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Regorafenib in combination with Radioembolization Group	Regorafenib	Participants in this group will receive combination therapy of Regorafenib and Yttrium 90 Trans-Arterial Radioembolization (Y90 TARE). Total participation duration is approximately 37 months.
Regorafenib in combination with Radioembolization Group	TheraSphere™ Yttrium-90 Trans-Arterial Radioembolization	Participants in this group will receive combination therapy of Regorafenib and Yttrium 90 Trans-Arterial Radioembolization (Y90 TARE). Total participation duration is approximately 37 months.

Primary Outcome Measures

Name	Time	Method
Disease Control Rate (DCR) Measured by Number of Participants	Up to 24 months	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.
Number of Participants Experiencing Treatment Related Adverse Events	Up to 25 months	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.
Number of Participants Experiencing Treatment Related Serious Adverse Events	Up to 25 months	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 36 months	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.
Time to Tumor Progression	Up to 36 months	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).
Duration of Overall Response (DOR)	Up to 36 months	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.
Progression-Free Survival (PFS)	Up to 36 months	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.
Overall Survival (OS)	Up to 36 months	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.

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States