TheraSphere + Immunotherapy for Liver Cancer

(ROWAN Trial)

Recruiting at 31 trial locations

Overseen By Maile Krumpschmidt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boston Scientific Corporation

Must be taking: Antiviral, Anti-HBV

Must not be taking: Immunosuppressants, Immune therapy

Disqualifiers: Metastases, Autoimmune disorders, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of the ROWAN clinical study is to assess the efficacy of local tumor control in HCC patients who receive TheraSphere followed by durvalumab and tremelimumab.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiviral treatment for hepatitis C, it should be stopped for at least 14 days before joining the study. Also, if you are using immunosuppressive medication, it should be stopped 14 days before the first dose of durvalumab, with some exceptions like certain steroids.

What data supports the effectiveness of the treatment TheraSphere Y-90 glass microsphere therapy for liver cancer?

Research shows that TheraSphere Y-90 microspheres are effective in treating liver cancer, particularly hepatocellular carcinoma (HCC), by delivering targeted radiation to tumors, which can help shrink them and improve survival rates. ^{1 2 3 4 5}

Is TheraSphere treatment safe for liver cancer?

TheraSphere treatment, which uses tiny glass beads with a radioactive substance, has been studied for liver cancer and shows a safety profile with fewer stomach and lung-related side effects compared to similar treatments. However, it can still cause some liver-related issues and other side effects like nausea and fluid buildup in the abdomen. ^{1 2 4 5 6}

How is the TheraSphere Y-90 treatment for liver cancer different from other treatments?

TheraSphere Y-90 treatment is unique because it involves injecting tiny glass beads containing a radioactive substance (yttrium-90) directly into the liver's blood vessels, allowing for targeted radiation therapy that minimizes damage to surrounding healthy tissue. This approach is particularly useful for liver tumors that cannot be surgically removed. ^{1 2 4 5 7}

Research Team

Aiwu Ruth He, MD PhD

Principal Investigator

Georgetown University

Beau Toskich, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults over 18 with Hepatocellular Carcinoma (HCC) who haven't had systemic HCC treatment, are ineligible for liver resection/ablation/transplantation, and have a tumor volume ≤35% of the liver. They must have adequate organ function, no severe hepatic vein invasion or extrahepatic metastases, and not be in another interventional study.

Inclusion Criteria

Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.

My kidney and bone marrow are working well.

At least 30% of my liver is healthy and functioning.

Exclusion Criteria

My liver imaging tests show specific findings.

Known allergy or hypersensitivity to any of the study drugs or excipients.

History of active primary/acquired immunodeficiency.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

TheraSphere Treatment

TheraSphere is administered to patients before the initiation of Durvalumab and Tremelimumab

1 week

1 visit (in-person)

Durvalumab and Tremelimumab Treatment

Participants receive Tremelimumab plus Durvalumab once, followed by monthly Durvalumab administration

18 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Durvalumab
• TheraSphere Y-90 glass microsphere therapy
• Tremelimumab

Trial Overview The ROWAN trial is testing TheraSphere Y-90 therapy followed by Durvalumab and Tremelimumab immunotherapies to see how well they control local tumor growth in patients with HCC. The effectiveness will be measured using specific imaging criteria.

Participant Groups

Group I: TheraSphere followed by Durvalumab and Tremelimumab Experimental Treatment 3 Interventions

TheraSphere followed by Tremelimumab plus Durvalumab administered once, then repeated administration of Durvalumab monthly up 18 months.

TheraSphere Y-90 glass microsphere therapy is already approved in United States, European Union for the following indications:

Approved in United States as TheraSphere Y-90 Glass Microspheres for:

• Unresectable hepatocellular carcinoma

Approved in European Union as TheraSphere Y-90 Glass Microspheres for:

• Hepatocellular carcinoma

Who Is Running the Clinical Trial?

Boston Scientific Corporation

Lead Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Biocompatibles UK Ltd

Industry Sponsor

Trials

25

Recruited

3,300+

Findings from Research

In a study involving 15 patients with primarily hepatic tumors, the use of (90)Y radiolabelled microspheres (TheraSphere) showed a promising therapeutic approach, with 14 patients treated and a response rate of partial response in 6 and stabilization in 5.

Despite some technical challenges during the procedure, the treatment resulted in low radiation exposure for the medical staff and highlighted the importance of SPECT/CT imaging in improving treatment planning and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience of hepatic radioembolization using microspheres labelled with yttrium-90 (TheraSphere): practical aspects concerning its implementation. Garin, E., Rolland, Y., Boucher, E., et al.[2021]

In a phase II study involving 27 patients with liver-dominant colorectal metastases, TheraSphere treatment demonstrated a high tumor response rate, with 88% response measured by PET imaging compared to only 35% by CT imaging.

The treatment was associated with minimal toxicity, with most side effects being mild and transient, suggesting that TheraSphere can effectively stabilize liver disease in patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging. Lewandowski, RJ., Thurston, KG., Goin, JE., et al.[2015]

Yttrium-90 (Y90) radioembolization therapy using TheraSphere® has been deemed safe and effective for treating hepatocellular carcinoma (HCC), even in patients with portal vein thrombosis, according to the Radioembolization Brachytherapy Oncology Consortium.

Despite promising initial results, there are currently no randomized clinical trials demonstrating a survival benefit for TheraSphere®, indicating the need for further research before it can be fully recommended as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioembolization for hepatocellular carcinoma using TheraSphere®. Ali, SM.[2021]

In a study of 88 patients with hepatocellular carcinoma treated with yttrium 90 microspheres (TheraSpheres), 42% experienced liver toxicities, with higher risks associated with elevated pretreatment total bilirubin levels and increased liver radiation doses.

Despite the occurrence of liver toxicities, most resolved over time, and no patients developed confirmed radiation-induced liver disease, indicating that doses up to 150 Gy for a single treatment and 268 Gy for repeated treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. Goin, JE., Salem, R., Carr, BI., et al.[2019]

In a study of 43 patients with unresectable hepatocellular carcinoma (HCC) treated with 90Y microspheres (TheraSphere) over 4 years, 47% showed a significant reduction in tumor size, and 79% had a positive tumor response when considering both size reduction and tumor necrosis.

The treatment was found to be safe, with no life-threatening adverse events reported, and median survival times varied significantly among risk groups, highlighting the potential effectiveness of this therapy for HCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. Salem, R., Lewandowski, RJ., Atassi, B., et al.[2022]

In a systematic review of 31 studies, TheraSphere® (glass) microspheres showed a safer profile than SIR-Spheres® (resin) microspheres for treating hepatocellular carcinoma, with fewer gastrointestinal and pulmonary adverse events reported.

Patients treated with resin microspheres experienced more severe adverse events, such as gastric ulcers and hepatic failure, while glass microspheres had a comparable safety profile regarding post-embolization syndrome outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review. Kallini, JR., Gabr, A., Thorlund, K., et al.[2019]

The glass microsphere TheraSphere, which delivers the beta-emitting isotope yttrium 90 (Y 90), was well tolerated in dogs even at doses up to 12 times the expected human dose, indicating a favorable safety profile for potential human use.

Hepatic arterial injection of radioactive TheraSphere resulted in significant localized radiation exposure without causing total liver necrosis or myelosuppression, suggesting that proposed human doses of 5000 to 10,000 cGy could be both feasible and tolerable for targeting liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of hepatic arterial yttrium 90 glass microspheres in dogs. Wollner, I., Knutsen, C., Smith, P., et al.[2019]

References

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

First experience of hepatic radioembolization using microspheres labelled with yttrium-90 (TheraSphere): practical aspects concerning its implementation. [2021]

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

90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging. [2015]

3. India pubmed.ncbi.nlm.nih.gov

Radioembolization for hepatocellular carcinoma using TheraSphere®. [2021]

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

Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. [2019]

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

Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. [2022]

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

Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review. [2019]

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

Effects of hepatic arterial yttrium 90 glass microspheres in dogs. [2019]