Regorafenib + Yttrium-90 for Liver Cancer

Overseen By Benjamin Spieler, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Antivirals, Anti-arrhythmics

Disqualifiers: Brain metastases, Major extrahepatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 25 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with liver cancer that cannot be removed by surgery. The researchers aim to evaluate the effects of combining Regorafenib, a medication, with Yttrium-90, a type of radiation treatment, on the cancer. The trial seeks participants diagnosed with liver cancer that cannot be surgically removed and who have not yet received systemic therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on blood thinners like warfarin or heparin, you can still participate as long as your blood clotting tests are normal.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that regorafenib, used as a second treatment option for liver cancer, has positive effects. Patients generally tolerated it well, though some experienced tiredness and skin reactions on their hands and feet.

Studies have found that Yttrium-90 radioembolization (also called TARE) is a safe and effective treatment for liver cancer, targeting the tumor directly in the liver. Some side effects can include mild tiredness and stomach pain, but these are usually manageable.

Combining these two treatments may improve response rates and extend the time patients live without their cancer worsening. Researchers are studying the combination to ensure its safety for patients, and early results are promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Regorafenib and Yttrium-90 because it offers a unique approach to treating liver cancer. Unlike traditional therapies that might involve surgery or chemotherapy, this treatment combines a targeted cancer drug, Regorafenib, with a specialized form of radiation called Yttrium-90 Trans-Arterial Radioembolization (Y90 TARE). This combination aims to attack cancer cells both systemically and directly within the liver, potentially increasing effectiveness and reducing side effects compared to conventional treatments. By using this dual approach, researchers hope to improve outcomes for patients who have limited options with existing therapies.

What evidence suggests that Regorafenib in combination with Yttrium-90 might be an effective treatment for liver cancer?

Research has shown that combining the drug Regorafenib with Yttrium-90 (Y-90) radioembolization may improve liver cancer treatment. This trial will administer this combination therapy to participants to evaluate its effectiveness. Studies have found that adding Y-90 radioembolization can shrink tumors and better control the disease. Previous results suggest that using both local (Y-90) and whole-body (Regorafenib) treatments together can lead to better outcomes and possibly longer survival. Additionally, Y-90 treatment has slowed disease progression. This combination therapy is being tested to determine if these benefits can be achieved in patients with liver cancer that cannot be surgically removed. ^{1 3 6 7 8}

Who Is on the Research Team?

Lynn G Feun, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Adults over 18 with unresectable hepatocellular carcinoma (HCC) who haven't had systemic therapy for HCC, meet specific blood test criteria, and can safely undergo radioembolization. They must agree to contraception requirements. Excluded are those with other cancers, significant heart disease, recent bleeding events or surgeries, uncontrolled hypertension, brain metastases, or active hepatitis requiring treatment.

Inclusion Criteria

Participant agrees to comply with contraception requirements as described in protocol

Specific serum bilirubin, AST, ALT, creatinine, INR/PTT, platelet count, hemoglobin, and ANC levels within defined ranges

I have not had any drug treatments for liver cancer.

Exclusion Criteria

Previously untreated or concurrent cancer except specific exceptions

I have a wound, ulcer, or bone fracture that hasn't healed.

I do not have a serious ongoing infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy of Regorafenib and Yttrium-90 Trans-Arterial Radioembolization (Y90 TARE)

Up to 25 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Regorafenib
• Yttrium-90 Radioembolization

Trial Overview The trial is testing the combination of Regorafenib (a cancer drug) and Yttrium-90 Trans-Arterial Radioembolization (a type of targeted radiation therapy), to see how well they work together in treating patients with liver cancer that cannot be removed by surgery.

How Is the Trial Designed?

Group I: Regorafenib in combination with Radioembolization Group Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

In a study of 51 patients with unresectable hepatocellular carcinoma (u-HCC) treated with regorafenib after failing sorafenib, the median survival time was 16.7 months, indicating that regorafenib can be an effective second-line treatment.

The study found that maintaining a favorable hepatic functional reserve during regorafenib treatment is crucial for improving prognosis, with patients who had better liver function before and during treatment experiencing significantly longer survival times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy including regorafenib for unresectable hepatocellular carcinoma: Effect of early relative changes in hepatic functional reserve after regorafenib administration on prognosis. Ochi, H., Tani, J., Tomonari, T., et al.[2021]

In a study of 36 patients with advanced hepatocellular carcinoma (HCC) who had previously progressed on sorafenib, regorafenib demonstrated acceptable safety with manageable side effects, including hand-foot skin reactions and diarrhea.

Regorafenib showed evidence of antitumor activity, with a median overall survival of 13.8 months and a median time to progression of 4.3 months, indicating it may be a viable treatment option for patients with HCC after first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Bruix, J., Tak, WY., Gasbarrini, A., et al.[2022]

A meta-analysis of 2,213 subjects from 14 trials revealed that regorafenib, an oral multi-kinase inhibitor, significantly increases the risk of hepatic toxicities, with notable elevations in liver enzymes such as AST (32% incidence) and ALT (27% incidence).

Patients treated with regorafenib showed a high-grade risk of bilirubin elevation (5%) and AST elevation (6%), indicating the need for regular monitoring of liver function during treatment to manage potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk of regorafenib-induced hepatotoxicity. Zhao, B., Zhao, H.[2019]

Regorafenib has demonstrated a median overall survival of 11.08 months in hepatocellular carcinoma patients who have failed sorafenib treatment, based on a meta-analysis of 809 patients from one randomized-controlled trial and seven non-randomized studies.

The treatment shows a disease control rate of 65.5% and is considered relatively safe, with common side effects including diarrhea, fatigue, and hand-foot skin reactions, making it a valuable option for patients with intermediate to advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. Facciorusso, A., Abd El Aziz, MA., Sacco, R.[2023]

Regorafenib is the first approved tyrosine kinase inhibitor for metastatic colorectal cancer, showing significant improvements in progression-free and overall survival in patients who had previously undergone multiple lines of chemotherapy and targeted therapies, based on results from two phase III trials.

While regorafenib has a safety profile similar to other tyrosine kinase inhibitors, it is associated with specific adverse events like hand-foot skin reaction and hypertension, which can be managed effectively through patient education and timely dose adjustments, allowing patients to continue benefiting from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving patient outcomes with regorafenib for metastatic colorectal cancer - patient selection, dosing, patient education, prophylaxis, and management of adverse events. Hofheinz, RD., Arnold, D., Kubicka, S., et al.[2015]

Regorafenib is an effective multikinase inhibitor that targets various tyrosine kinases involved in cancer, leading to its approval as a second-line treatment for advanced hepatocellular carcinoma (HCC) and a third-line treatment for colorectal cancer (CRC) and gastrointestinal stromal tumors (GISTs).

Research indicates that while regorafenib shows beneficial effects in treating these cancers, there is a potential loss of sensitivity in tumor cells, prompting investigations into combining regorafenib with other therapies to enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumoral activity of single and combined regorafenib treatments in preclinical models of liver and gastrointestinal cancers. Fondevila, F., Méndez-Blanco, C., Fernández-Palanca, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06902246

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

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-06212

Regorafenib and Yttrium-90 Transarterial ... This phase II trial tests the safety and side effects of regorafenib in combination with yttrium-90 (Y-90) transarterial radioembolization (TARE) and how ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9606085/

Addition of Y-90 radioembolization increases tumor response ... Addition of Y-90 radioembolization increases tumor response and local disease control in hepatocellular carcinoma patients receiving sorafenib.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.e16633

Long-term outcome analysis of Y90 radioembolization in ... Multiple trials have evaluated the efficacy of Y90 in HCC; few have assessed long term hepatic function. These studies reported PFS ranging from ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/20101058231154666

Review of outcomes of combination therapy using yttrium ... The combination of local and systemic therapies demonstrated potential results for increased response rates, OS and PFS benefits.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772694/

Efficacy and safety of regorafenib as second-line treatment for ... It can be seen from our study that regorafenib, as a second-line treatment drug for liver cancer, still has a good effect on patients with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1051044324003981

Multidisciplinary Delphi Consensus on Safety of ... A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies.

8. wjgnet.com wjgnet.com/1949-8470/full/v16/i10/512.htm

Yttrium-90 radioembolization treatment strategies for ... This comprehensive review explores Yttrium-90 transarterial radioembolization (TARE) as an effective locoregional therapy for hepatocellular carcinoma across ...