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

28 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Regorafenib for liver cancer?

Research shows that Regorafenib, when used as a second-line treatment for liver cancer, can improve survival rates. In a study, patients taking Regorafenib lived longer (10.6 months) compared to those who took a placebo (7.8 months). ^{1 2 3 4 5}

Is the combination of Regorafenib and Yttrium-90 safe for liver cancer treatment?

Regorafenib has been studied for safety in liver cancer and other conditions, showing common side effects like hand-foot skin reaction, high blood pressure, fatigue, diarrhea, and liver issues. Regular liver function tests are recommended due to the risk of liver toxicity. While specific data on the combination with Yttrium-90 is not available, Regorafenib alone has a known safety profile. ^{1 6 7 8 9}

What makes the treatment Regorafenib + Yttrium-90 unique for liver cancer?

Regorafenib is a drug that targets specific proteins involved in cancer growth and blood vessel formation, and it is used as a second-line treatment for liver cancer when other treatments fail. Combining it with Yttrium-90, a type of radiation therapy, may enhance its effectiveness by directly targeting cancer cells in the liver, offering a novel approach compared to standard treatments. ^{1 3 10 11 12}

What is the purpose of this trial?

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.

Research Team

Lynn G Feun, MD

Principal Investigator

University of Miami

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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). 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

Findings from Research

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]

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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Immunotherapy combination with regorafenib for refractory hepatocellular carcinoma: A real-world study. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Regorafenib for the treatment of hepatocellular carcinoma. [2019]

3. Netherlands 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. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Sequential Treatment of Sorafenib-Regorafenib Versus Sorafenib-Physician's Choice: A Propensity Score-Matched Analysis. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. [2022]

7. Switzerland 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. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Incidence and risk of regorafenib-induced hepatotoxicity. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Anti-tumoral activity of single and combined regorafenib treatments in preclinical models of liver and gastrointestinal cancers. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Prognostic Factors of Regorafenib in the Treatment of BCLC Stage C Hepatocellular Carcinoma After Failure of the First-Line Therapy. [2023]