Liver-Directed Therapies vs. Radiation Therapy for Liver Cancer

Recruiting at1 trial location

Overseen by Manisha Palta, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Duke University

Must not be taking: Systemic therapy

Disqualifiers: Child Pugh C, Ascites, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a research study to evaluate change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30), from baseline to 1 month post treatment in two patient cohorts receiving Interventional Radiology Liver Directed Therapies or Hypofractionated Image-Guided Radiation Therapy.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you are currently receiving systemic therapy for liver cancer.

What data supports the effectiveness of the treatment for liver cancer?

Research shows that Selective Internal Radiation Therapy (SIRT) using yttrium-90 microspheres can effectively target liver tumors, as seen in studies with colorectal cancer liver metastases and hepatocellular carcinoma, improving outcomes when other treatments have failed. ^{1 2 3 4 5}

Is selective internal radiation therapy (SIRT) with yttrium-90 microspheres safe for humans?

SIRT with yttrium-90 microspheres is generally safe for humans, but it can have mild and temporary side effects. There are risks of serious complications like radiation-induced liver disease and tissue damage if the microspheres enter non-target areas, but these can be minimized with careful planning and technique. ^{1 6 7 8 9}

How does the treatment for liver cancer using yttrium-90 microspheres differ from other treatments?

This treatment, known as Selective Internal Radiation Therapy (SIRT), is unique because it delivers high doses of radiation directly to liver tumors using tiny radioactive beads called yttrium-90 microspheres. Unlike traditional radiation therapy, which affects a broader area, SIRT targets the liver tumors specifically, potentially reducing damage to surrounding healthy tissue. ^{2 3 6 10 11}

Research Team

Manisha Palta, MD

Principal Investigator

Duke Health

Eligibility Criteria

This trial is for adults with liver cancer (Hepatocellular Carcinoma) who are in relatively good health, have a specific score indicating their liver's condition (Child Pugh A5 to B8), and have up to 3 treatable lesions no larger than 5cm. It excludes those with more advanced liver issues, prior liver radiation unless approved by the lead researcher, current systemic cancer therapy, or unstable fluid accumulation in the abdomen.

Inclusion Criteria

My liver cancer diagnosis was confirmed by a biopsy or specific liver imaging.

My liver lesion can be treated with targeted radiology and high-intensity radiation.

My liver function score is within a mild to moderate range.

Exclusion Criteria

I have had liver radiation but got approval from the principal investigator.

Inability to complete baseline Quality of Life survey forms

My liver disease is severe.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Interventional Radiology Liver Directed Therapies or Hypofractionated Image-Guided Radiation Therapy

3-10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Quality of life questionnaires (Behavioural Intervention)

Trial Overview The study aims to assess changes in patients' quality of life after receiving either Interventional Radiology Liver Directed Therapies or Hypofractionated Image-Guided Radiation Therapy. Quality of life will be measured using EORTC C-30 questionnaires before and one month after treatment.

Participant Groups

Group I: Interventional Radiology Liver Directed Therapies (ILDT) Active Control 1 Intervention

ILDT includes ablations such as microwave ablation and percutaneous local ablation and embolotherapies including bland embolization, chemoembolization and radioembolization.

Group II: Hypofractionated Image-Guided Radiation Therapy (HIGRT) Active Control 1 Intervention

HIGRT is a non-invasive, outpatient procedure typically delivered in 3-10 fractions of radiation.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Mary E. Klotman

Duke University

Chief Executive Officer since 2017

MD from Duke University School of Medicine

Michelle McMurry-Heath

Duke University

Chief Medical Officer since 2020

MD from Duke University School of Medicine

Findings from Research

Selective internal radiation therapy (SIRT) using yttrium-90 microspheres was well tolerated in 19 patients with liver-predominant colorectal cancer, showing only a 15.8% incidence of grade 3 toxicity and no cases of radiation-induced liver disease.

The treatment resulted in a median overall survival of 14.9 months, indicating its potential as an effective salvage therapy for patients who had previously undergone multiple lines of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy. Sofocleous, CT., Garcia, AR., Pandit-Taskar, N., et al.[2022]

In a study involving 399 patients with chemotherapy-refractory colorectal cancer liver metastases, selective internal radiation therapy (SIRT) combined with standard care resulted in a median overall survival of 7.6 months, indicating its potential effectiveness as a treatment option.

The treatment was associated with manageable safety, as 143 patients experienced adverse events, with only 8% classified as grade 3, suggesting that SIRT is a relatively safe intervention for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of a National Programme for Selective Internal Radiation Therapy for Colorectal Cancer Liver Metastases. White, J., Carolan-Rees, G., Dale, M., et al.[2022]

In a trial involving 21 patients with advanced colorectal liver metastases, adding SIR-Spheres to standard chemotherapy significantly improved the response rate and time to disease progression, with a response rate of 90.9% compared to 0% in the chemotherapy-only group.

Patients receiving the combination treatment had a median survival of 29.4 months, compared to 12.8 months for those on chemotherapy alone, indicating that SIR-Spheres can enhance survival outcomes despite a higher incidence of severe toxicity events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. Van Hazel, G., Blackwell, A., Anderson, J., et al.[2022]

In a phase 2 trial involving 42 patients with unresectable hepatocellular carcinoma (uHCC), the combination of selective internal radiation therapy (SIRT) and the PD-1 inhibitor nivolumab demonstrated an acceptable safety profile, with 41 patients experiencing adverse events, but only a small number facing severe complications.

The treatment showed promising efficacy, with an objective response rate of 41.5%, a median time to progression of 8.8 months, and a median overall survival of 20.9 months, indicating potential benefits for patients ineligible for chemoembolization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study. de la Torre-Aláez, M., Matilla, A., Varela, M., et al.[2023]

In a study of 226 patients with unresectable hepatocellular carcinoma treated with yttrium-90 resin microspheres (Y90 SIRT), the median overall survival was 16.6 months, indicating that this treatment can be effective for extending life in these patients.

Factors such as bilobar disease, higher baseline albumin-bilirubin scores, and prior treatment with sorafenib were linked to shorter survival, while successful liver transplantation in some patients was associated with longer survival, highlighting the importance of considering these factors in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors of unresectable hepatocellular carcinoma treated with yttrium-90 radioembolization: results from a large cohort over 13 years at a single center. Shah, RM., Sheikh, S., Shah, J., et al.[2022]

Selective internal radiation therapy (SIRT) using (90)yttrium microspheres is effective for treating non-resectable liver tumors, showing measurable tumor responses or delayed disease progression in most patients with hepatocellular carcinoma or colorectal cancer metastases.

While SIRT is generally safe with most adverse events being mild, there are risks of serious complications, such as radiation-induced tissue damage, which can be minimized to less than 10% through careful patient selection and precise technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancer. Wang, SC., Bester, L., Burnes, JP., et al.[2016]

In a study of 21 patients treated with 90Y microspheres for extensive liver tumors, only four patients experienced moderate adverse effects, including cholecystitis, peptic ulceration, and radiation hepatitis, all of which were manageable with appropriate therapy.

The findings emphasize the importance of careful patient selection and thorough pre-treatment evaluations to minimize the risk of adverse effects during selective internal radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management and prevention of adverse effects related to treatment of liver tumours with 90Y microspheres. Szyszko, T., Al-Nahhas, A., Tait, P., et al.[2006]

In a randomized controlled trial involving 424 patients with advanced hepatocellular carcinoma (HCC), the combination of selective internal radiation therapy (SIRT) and sorafenib did not significantly improve overall survival compared to sorafenib alone, with median survival times of 12.1 months versus 11.4 months, respectively.

Subgroup analyses suggested potential benefits of the SIRT plus sorafenib combination for specific patient groups, such as those without cirrhosis or younger than 65 years, indicating that further research could explore these findings in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. Ricke, J., Klümpen, HJ., Amthauer, H., et al.[2021]

In a phase 3 trial involving 467 patients with advanced hepatocellular carcinoma, sorafenib showed a median overall survival of 9.9 months, while selective internal radiotherapy (SIRT) with yttrium-90 had a median survival of 8.0 months, indicating no significant difference in survival between the two treatments (p=0.18).

Both treatments had high rates of serious adverse events, with 77% of patients in the SIRT group and 82% in the sorafenib group experiencing at least one serious side effect, suggesting that safety profiles should be considered alongside efficacy when choosing a treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Vilgrain, V., Pereira, H., Assenat, E., et al.[2022]

In a study of 21 patients with liver tumors treated with yttrium-90 microspheres, the therapy showed potential as an alternative treatment, but safety concerns were noted, including one case of mortality due to fulminant hepatic failure.

The treatment was associated with some morbidities, such as radiation hepatitis in one patient and peptic ulcer disease in six patients, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The toxicity of liver directed yttrium-90 microspheres in primary and metastatic liver tumors. Neff, R., Abdel-Misih, R., Khatri, J., et al.[2008]

In a study of 111 patients with unresectable hepatocellular carcinoma (HCC) treated with Y-90 resin microspheres, factors such as early-stage disease and absence of complications like portal vein thrombosis were linked to significantly longer overall survival, with patients in the early-stage group living an average of 27.8 months compared to just 9.2 months for those in advanced stages.

Y-90 resin treatment was generally well-tolerated, with adverse events reported in 23 patients shortly after treatment and 46 patients at 3 months, indicating that while some side effects occurred, the therapy was manageable and could be an effective option for bridging patients to liver transplantation, which further improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study. Mantry, PS., Mehta, A., Madani, B., et al.[2022]

References

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

Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Analysis of a National Programme for Selective Internal Radiation Therapy for Colorectal Cancer Liver Metastases. [2022]

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

Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Prognostic factors of unresectable hepatocellular carcinoma treated with yttrium-90 radioembolization: results from a large cohort over 13 years at a single center. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancer. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Management and prevention of adverse effects related to treatment of liver tumours with 90Y microspheres. [2006]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The toxicity of liver directed yttrium-90 microspheres in primary and metastatic liver tumors. [2008]

11. China pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study. [2022]