TheraSphere + Immunotherapy for Liver Cancer

(ROWAN Trial)

Not currently recruiting at 47 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a treatment called TheraSphere, followed by two immunotherapy drugs, in controlling liver cancer tumors. TheraSphere uses tiny glass beads to deliver radiation directly to liver tumors, while the immunotherapies, durvalumab (Imfinzi) and tremelimumab (Imjudo), enhance the immune system's ability to fight cancer. Individuals with liver cancer that cannot be removed by surgery or other treatments may qualify if their tumor occupies 35% or less of their liver. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that TheraSphere Y-90 glass microsphere therapy is generally well-tolerated. This treatment targets liver cancer by using tiny glass beads to deliver radiation directly to the tumor, reducing exposure to the rest of the body. The radiation from these beads decreases significantly within two weeks after treatment.

Studies have examined the safety of combining durvalumab and tremelimumab. Research indicates that patients receiving this combination can experience side effects, with some experiencing severe reactions. However, these treatments have also helped control cancer growth in some liver cancer patients.

Considering the benefits and risks of joining a trial is important. These treatments are in a trial phase to assess their efficacy and safety, meaning they have shown some safety evidence, but more information is being collected. Always discuss with a healthcare provider to understand what these findings could mean. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for liver cancer, which often include surgery, chemotherapy, and radiofrequency ablation, TheraSphere with immunotherapy combines a targeted radiation method with immune-boosting drugs. TheraSphere uses Y-90 glass microspheres to deliver radiation directly to the tumor, minimizing damage to surrounding healthy tissue. Researchers are excited because when combined with the immunotherapy drugs Durvalumab and Tremelimumab, it not only targets the cancer more precisely but also enhances the body's immune response against cancer cells. This dual approach has the potential to improve outcomes by attacking the cancer on multiple fronts.

What evidence suggests that TheraSphere followed by durvalumab and tremelimumab could be effective for liver cancer?

Research has shown that TheraSphere Y-90 effectively treats liver cancer, achieving high survival rates in patients at various stages of the disease. Over 100,000 patients worldwide have received this treatment, demonstrating its reliability.

Studies on the combination of durvalumab and tremelimumab have shown promising results. Durvalumab alone has controlled the disease and improved outcomes for liver cancer patients. When combined with tremelimumab, it has led to remarkable survival rates, with one in five patients living for five years.

In this trial, participants will receive TheraSphere followed by durvalumab and tremelimumab, which could effectively control liver cancer tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Aiwu Ruth He, MD PhD

Principal Investigator

Georgetown University

Beau Toskich, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05027425

Study Details | NCT05027425 | Durvalumab (MEDI4736) ... Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS630

Phase II trial of durvalumab (MEDI4736) with/without ... Phase II trial of durvalumab (MEDI4736) with/without tremelimumab for advanced hepatocellular carcinoma after palliative hypofractionated radiotherapy.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6738201/

Immuno-Oncology Therapy for Hepatocellular Carcinoma Although only 30 patients were evaluated for safety and efficacy, the ORR per RECIST 1.1 was 53.3%, the disease control rate was 90.0%, and 6.7% ...

4. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/imfinzi-plus-imjudo-demonstrated-unprecedented-overall-survival-alc-with-one-in-five-patients-surviving-five-years-himalaya-phase-iii-trial.html

Imfinzi plus Imjudo demonstrated unprecedented overall ... Imfinzi plus Imjudo demonstrated unprecedented overall survival in advanced liver cancer with one in five patients surviving five years in ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT434862

Phase I/II clinical trial of regorafenib plus durvalumab ... Objective response rates also showed improvement, with 26.7% for durvalumab and 18.7% for placebo.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06911255

Safety and Efficacy of Tremelimumab+Durvalumab ... The purpose of this clinical trial is to evaluate the safety and efficacy of tremelimumab + durvalumab administered concurrently with transarterial ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9637844/

Liver injury during durvalumab-based immunotherapy is ... Durvalumab given in combination with cytotoxic chemotherapy resulted in the highest rate of liver injury (71.4%% vs. 29.7%) compared to when it was given alone ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/study/NCT05027425

Study Details | NCT05027425 | Durvalumab (MEDI4736) ... Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver ...

9. jitc.bmj.com jitc.bmj.com/content/13/5/e011140

Differential safety profiles of durvalumab monotherapy and ... Results Compared with D monotherapy, patients treated with D+T had higher incidences of maximum grade 3 or 4 AEs (49.5% vs 39.6%), treatment- ...

10. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/520275

Study of Tremelimumab and Durvalumab ... - Carebox Connect It can be used to predict the prognosis of patients with liver cirrhosis and hepatocellular carcinoma, and has been shown to be more accurate ...