Liver-Directed Therapies vs. Radiation Therapy for Liver Cancer

Recruiting at 1 trial location

Overseen By Linda Kaltenbach, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Systemic therapy

Disqualifiers: Child Pugh C, Ascites, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3-10 weeks

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two different treatments for liver cancer affect patients' quality of life. One group receives liver-directed therapies, such as targeted treatments that directly impact liver tumors. The other group undergoes a type of radiation therapy known as Y-90 radioembolization or Selective Internal Radiation Therapy (SIRT), which is precise and administered in several sessions. Suitable candidates have been diagnosed with liver cancer, have up to three liver tumors, each no larger than 5 cm, and can undergo both types of treatment. As an unphased trial, this study offers a unique opportunity to advance liver cancer treatment options.

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.

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

Research has shown that treatments like Interventional Radiology Liver Directed Therapies (ILDT), including ablations and embolotherapies, succeed in treating liver cancer. Patients receiving these treatments often experience good survival rates. However, some procedures, such as radiofrequency ablation, carry a risk of cancer cell spread.

Conversely, Hypofractionated Image-Guided Radiation Therapy (HIGRT) is considered a safe option for liver cancer. Studies suggest it is effective with manageable side effects. This non-invasive therapy is administered in several sessions, offering convenience for patients.

Both treatment options have demonstrated safety in previous studies. It is important to consult with a healthcare provider to determine the most suitable treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different liver-directed therapies stack up against radiation therapy for liver cancer. Interventional Radiology Liver Directed Therapies (ILDT) includes advanced techniques like microwave ablation and embolotherapies, which directly target liver tumors with precision, potentially sparing surrounding healthy tissue. Hypofractionated Image-Guided Radiation Therapy (HIGRT), on the other hand, offers a non-invasive option that can be delivered in just a few outpatient sessions. This trial could reveal which method better enhances quality of life and effectiveness, offering new hope for patients with liver cancer.

What evidence suggests that this trial's treatments could be effective for liver cancer?

This trial will compare liver-directed therapies with hypofractionated image-guided radiation therapy (HIGRT) for liver cancer. Research has shown that liver-directed treatments, such as microwave ablation and chemoembolization, can extend the lives of liver cancer patients and usually result in fewer side effects compared to other options. These treatments are particularly effective when surgery isn't possible.

HIGRT, another treatment option in this trial, is a non-invasive method that can be completed in just a few sessions. Evidence indicates that HIGRT effectively controls tumor growth, with high rates of keeping the cancer in check and reasonable survival times. Both treatment options in this trial offer hope for better outcomes for liver cancer patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Manisha Palta, MD

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Quality of life questionnaires

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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]

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]

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 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 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 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]

Citations

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Efficacy and safety of image-guided hypofractionated ... These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879850025002012

Long-Term Outcome of Stereotactically Designed ... Stereotactic body radiation therapy (SBRT) has emerged as a promising local treatment for small, early-stage HCCs, with reported 2-year local ...

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Efficacy and safety of image-guided hypofractionated ... The 1-year local control rate was 87%, and the median survival was 17 months. However, there were 7 treatment-related deaths, including 5 cases ...

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Long-term outcomes of the 2-week schedule of ... - BMC Cancer The 3- and 5-year overall survival rates were 52.3% and 40.9%, respectively, and local control rates were 79.5% and 72.6% in all treated lesions ...

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Evidence-based clinical recommendations for ... Hypofractionated radiotherapy is particularly effective for primary and metastatic liver cancer where high-dose irradiation is crucial to ...

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Efficacy and safety of image-guided hypofractionated ... These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56–75 Gy 10 ) is a feasible treatment option for PVTT in HCC patients.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04933435

Interventional Radiology Liver Directed Therapies and ... 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 ...