Therasphere + Systemic Therapy for Liver Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: PDL1, PD-1 antagonists

Disqualifiers: Autoimmune disease, CNS metastases, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

84 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to compare progression free survival between two available systemic therapies - immunotherapy and tyrosine kinase inhibitors - after Therasphere® (yttrium-90) treatment in adult patients with advanced hepatocellular carcinoma. The immunotherapy consists of a standard-of-care treatment with Atezolizumab and Bevacizumab. Treatment with tyrosine kinase inhibitors consists of standard-of-care Lenvatinib or Cabozantinib.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on any investigational agents, certain cancer therapies, or systemic glucocorticoids within specific timeframes before registration. It's best to discuss your current medications with the trial team.

What data supports the idea that Therasphere + Systemic Therapy for Liver Cancer is an effective treatment?

The available research shows that combining atezolizumab and bevacizumab, which are drugs used in systemic therapy, is effective for treating advanced liver cancer. Studies have compared this combination to another drug called lenvatinib. While the results are mixed, the combination of atezolizumab and bevacizumab is often used as a first choice for treatment. This suggests that it is considered effective by many doctors, even though there is no clear winner between the two options. ^{1 2 3 4 5}

What safety data exists for Therasphere + Systemic Therapy for liver cancer?

The safety of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib has been evaluated in several studies for the treatment of unresectable hepatocellular carcinoma (HCC). These studies, including retrospective and meta-analysis, have compared the safety profiles of these treatments. The findings suggest that both atezolizumab plus bevacizumab and lenvatinib have been used as first-line therapies with similar safety profiles in real-world scenarios. However, specific safety data for Therasphere (Yttrium-90 glass microspheres) combined with these systemic therapies is not directly addressed in the provided research abstracts. ^{1 2 5 6 7}

Is the drug combination of Atezolizumab and Bevacizumab, Lenvatinib, or Cabozantinib promising for liver cancer?

Yes, the drug combination of Atezolizumab and Bevacizumab is promising for liver cancer. It is considered a standard first-line treatment for unresectable liver cancer, showing similar effectiveness to Lenvatinib, another leading option. This combination is widely used and has been studied in real-world settings, indicating its potential as an effective treatment. ^{1 3 5 7 8}

Research Team

Aparna Kalyan

Principal Investigator

Northwestern University

Eligibility Criteria

Adults with advanced hepatocellular carcinoma (liver cancer) who are not candidates for transplant or surgery. They must have a good performance status, measurable disease, and well-managed HIV or hepatitis if present. Women of childbearing age and sexually active men must use two contraception methods. Excluded are those with recent cancers, dialysis patients, untreated brain metastases, vaccine recipients within 28 days, pregnant/nursing women, allergy to trial drugs/components, prior PD-1/PD-L1 therapy users.

Inclusion Criteria

I have HIV and am on effective treatment.

I may or may not have received previous treatments for my condition.

I have liver cancer with a mild to moderate liver function score.

Exclusion Criteria

I have or had an autoimmune disease that could come back.

I have not received a live vaccine in the last 28 days.

I have brain metastases that have not been treated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Therasphere® (Yttrium-90) Treatment

Participants receive liver-directed therapy with Therasphere® (Y-90) following institutional procedures

1 day

1 visit (in-person)

Recovery

Participants have a recovery period after Y-90 treatment before starting systemic therapy

2-3 weeks

Systemic Therapy

Participants receive systemic therapy with either immunotherapy (atezolizumab + bevacizumab) or TKI treatment (lenvatinib or cabozantinib)

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Atezolizumab and Bevacizumab
• Lenvatinib or Cabozantinib
• Y90

Trial Overview The study compares the effectiveness of Therasphere® (Y90 radiotherapy) followed by either immunotherapy (Atezolizumab + Bevacizumab) or tyrosine kinase inhibitors (Lenvatinib/Cabozantinib). The goal is to see which treatment better prevents liver cancer from progressing.

Participant Groups

Group I: Y90 + TKI Experimental Treatment 1 Intervention

Group II: Y90 + Atezolizumab and Bevacizumab Experimental Treatment 1 Intervention

Atezolizumab and Bevacizumab is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in Canada as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Approved in Japan as Tecentriq and Avastin for:

• Hepatocellular carcinoma
• Non-small cell lung cancer
• Triple-negative breast cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Atezolizumab plus bevacizumab significantly improves progression-free survival (PFS) compared to lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC), based on a meta-analysis of 8 studies involving 3690 patients.

Patients receiving atezolizumab plus bevacizumab experience fewer severe adverse events (grade 3/4) compared to those treated with lenvatinib, indicating a better safety profile, although lenvatinib may be more effective for overall survival in non-viral patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Liu, J., Yang, L., Wei, S., et al.[2023]

In a systematic review of 8 studies involving 6628 patients with advanced hepatocellular carcinoma (HCC), no significant differences in overall survival (OS) or progression-free survival (PFS) rates were found between the treatment options of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib.

However, Atez/Bev was more beneficial for patients with HCC caused by viral hepatitis, while lenvatinib showed better outcomes for patients with Child-Pugh class B liver function, indicating that treatment effectiveness may vary based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis. Du, S., Cao, K., Wang, Z., et al.[2023]

In a study of 13 patients, rechallenging with lenvatinib after treatment with atezolizumab plus bevacizumab showed anti-tumor effects, but the duration of the second lenvatinib treatment was significantly shorter (2.8 months) compared to the first treatment (8.7 months).

While lenvatinib re-administration can be effective, it may lead to deterioration in liver function, highlighting the need for careful monitoring of liver health and patient status during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma. Komatsu, S., Yano, Y., Kido, M., et al.[2022]

In a review of 8 studies comparing atezolizumab plus bevacizumab (ATE/BEV) to lenvatinib (LEN) for advanced hepatocellular carcinoma, both treatments showed similar effectiveness in terms of objective response rate (ORR) and disease control rate (DCR).

While LEN was found to be non-inferior to ATE/BEV regarding progression-free survival (PFS), it may carry a higher risk of adverse events, suggesting that while both treatments are effective, LEN could lead to more side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis. Giri, S., Angadi, S., Vaidya, A., et al.[2023]

In a study of 2205 patients with unresectable HCC, there was no significant overall survival advantage for atezolizumab plus bevacizumab compared to lenvatinib, indicating similar efficacy in first-line treatment.

However, the safety profile favored atezolizumab plus bevacizumab, as it had fewer adverse events, and specific patient groups showed differential benefits, with lenvatinib being more effective for those with non-alcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Casadei-Gardini, A., Rimini, M., Tada, T., et al.[2023]

In a study of 139 advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib, the efficacy in terms of objective response rate and progression-free survival was similar for patients with viral and nonviral infections, indicating that lenvatinib is effective regardless of the infection type.

The 1-year survival rates were 68.7% for patients with viral infections and 59.5% for those with nonviral infections, suggesting that while there is a difference in survival rates, lenvatinib remains a viable treatment option for both groups without significant differences in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study. Hatanaka, T., Kakizaki, S., Nagashima, T., et al.[2021]

In a study of 92 patients with unresectable hepatocellular carcinoma (HCC), lenvatinib showed similar efficacy to the combination of atezolizumab and bevacizumab (A+B) in terms of objective response rate, progression-free survival, and overall survival, indicating that both treatments are viable first-line options.

The safety profiles of lenvatinib and A+B were comparable, with similar rates of adverse events and minimal impact on liver function, suggesting that both therapies are safe for patients with HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. Su, CW., Teng, W., Lin, PT., et al.[2023]

In a study of 66 Taiwanese patients with advanced-stage hepatocellular carcinoma (HCC), those treated with lenvatinib showed a higher objective response rate (ORR) of 36.4% compared to 11.4% for sorafenib, indicating better efficacy for lenvatinib.

Both treatments resulted in similar median overall survival (OS) times (9.36 months for lenvatinib vs. 8.36 months for sorafenib), but patients on lenvatinib who achieved an objective tumor response had a significantly improved OS of 11.29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population. Lee, SW., Yang, SS., Lien, HC., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023]

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

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis. [2023]

3. Greece pubmed.ncbi.nlm.nih.gov

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma. [2022]

4. Poland pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study. [2021]

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

Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population. [2022]