Combined Y-90 SIRT + SBRT for Liver Cancer

Overseen By Cancer AnswerLine

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Michigan Rogel Cancer Center

Disqualifiers: Pregnancy, Allergy to contrast, others

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

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

Compensation: Varies

Number of Visits: 1

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for liver cancer by combining two existing radiation techniques: Y-90 SIRT (Selective Internal Radiation Therapy), which delivers radiation directly to liver cancer cells, and SBRT (Stereotactic Body Radiation Therapy), a type of focused radiation. Researchers aim to determine the safety of using these treatments together and to learn about any side effects. This trial targets individuals with liver cancer that cannot be surgically removed or has spread from other parts of the body, and who have at least one liver tumor larger than 2 cm or 4 cc in size. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that Yttrium-90 (Y-90) Selective Internal Radiation Therapy (SIRT) is generally safe for treating liver cancer. Many studies indicate that Y-90 SIRT effectively controls liver tumors without causing serious side effects, and patients usually tolerate the treatment well.

For Stereotactic Body Radiation Therapy (SBRT), research finds it provides strong control over liver cancer and often leads to long-term survival for many patients. Importantly, it carries a lower risk of severe side effects compared to other treatments, such as surgery.

Both Y-90 SIRT and SBRT have been proven safe individually. This study will test their combined effectiveness and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for liver cancer?

Unlike the standard treatments for liver cancer, which often include surgery, chemotherapy, and traditional radiation therapy, the combination of Yttrium-90 SIRT and SBRT offers a unique approach. Yttrium-90, a radioactive substance, is used in Selective Internal Radiation Therapy (SIRT) to directly target liver tumors, delivering radiation from inside the body with precision. This internal targeting can potentially minimize damage to surrounding healthy tissue compared to external radiation methods. Following SIRT with Stereotactic Body Radiation Therapy (SBRT), which provides high doses of radiation with pinpoint accuracy, could further enhance tumor control. Researchers are excited about this approach because the combination of internal and external precision radiation may improve treatment effectiveness and reduce side effects.

What evidence suggests that this combination therapy could be effective for liver cancer?

This trial will evaluate the combination of Yttrium-90 (Y-90) Selective Internal Radiation Therapy (SIRT) followed by Stereotactic Body Radiation Therapy (SBRT) for liver cancer. Research has shown that Y-90 SIRT effectively manages liver tumors, often leading to significant tumor shrinkage when surgery isn't possible. Specifically, patients receiving Y-90 SIRT had a median survival time of nearly two years. SBRT has also succeeded in treating liver cancer, effectively targeting the tumor area, with long-term studies showing control of liver cancer for up to five years in many patients without severe side effects. This trial aims to enhance these positive effects by combining Y-90 SIRT and SBRT, potentially offering a stronger treatment option for liver cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Kyle C. Cuneo

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with unresectable hepatocellular carcinoma (liver cancer) that meets specific imaging criteria, has a life expectancy of at least 6 months, and agrees to use contraception. It excludes those who can't stay still for scans, are pregnant or refuse birth control, have certain allergies or contraindications to MRI contrast agents or Theraspheres, high bilirubin levels, main portal vein occlusion, excessive lung shunting from the liver.

Inclusion Criteria

Patients must have a life expectancy of at least 6 months.

I agree to use effective birth control during and for 3 months after the study.

I do not have untreated cancer outside of my liver.

Exclusion Criteria

My main portal vein is blocked.

Patients with an allergy or contraindication to MRI on MRI contrast (Eovist or Gadolinium)

My bilirubin levels did not significantly increase after Y90 treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Y-90 SIRT Treatment

Participants receive Y-90 Selective Internal Radiation Therapy (SIRT) to deliver radiation internally to the tumor

1 week

1 visit (in-person)

SBRT Treatment

Participants receive Stereotactic Body Radiation Therapy (SBRT) targeting areas of tumors not fully treated by Y-90 SIRT

1-2 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of overall survival and progression

Up to 5 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PET/CT
• Selective Internal Radiation Therapy
• Stereotactic Body Radiation Therapy
• Yttrium-90

Trial Overview The study tests combining Y-90 Selective Internal Radiation Therapy (SIRT) with Stereotactic Body Radiation Therapy (SBRT) in treating liver cancer. This approach is being evaluated for safety and side effects; it's also the first time Y-90 PET/CT imaging will be used in planning SBRT.

How Is the Trial Designed?

Group I: Y-90 SIRT followed by SBRT Experimental Treatment 5 Interventions

Y-90 SIRT followed by SBRT

Yttrium-90 is already approved in United States, European Union for the following indications:

Approved in United States as Y-90 for:

• Hepatocellular carcinoma
• Colorectal cancer liver metastases

Approved in European Union as Y-90 for:

• Hepatocellular carcinoma
• Colorectal cancer liver metastases

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

Published Research Related to This Trial

Yttrium-90 radiation segmentectomy (90Y RS) demonstrated a high disease control rate of 93.3% in 16 patients with oligometastatic secondary hepatic malignancies, indicating its efficacy in managing this condition.

The treatment exhibited an excellent safety profile, with only one patient experiencing Grade 3 toxicities and no Grade 4 toxicities reported, suggesting that 90Y RS is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 Radiation Segmentectomy in Oligometastatic Secondary Hepatic Malignancies. Chiu, AM., Savoor, R., Gordon, AC., et al.[2023]

In a study of 17 patients with unresectable and metastatic intrahepatic cholangiocarcinoma (ICC) treated with Yttrium-90 (Y-90), the five-year overall survival rate was 26.8%, with a median survival of 33.6 months, indicating promising efficacy.

The treatment was found to be safe, with no 90-day mortality reported and only two complications noted, suggesting that Y-90 could be a viable option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma? Shaker, TM., Chung, C., Varma, MK., et al.[2019]

Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is an effective and safe minimally invasive treatment for liver malignant tumors, supported by clinical applications over the past two decades and recognized by major cancer treatment guidelines.

A consensus was formed by experts from various medical fields to standardize the management and treatment procedures for (90)Y-SIRT, addressing critical aspects such as indications, contraindications, postoperative follow-up, and radiation safety, to enhance treatment safety and success rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma]. [2021]

In a study involving 30 patients with unresectable hepatocellular carcinoma (HCC) and portal vein thrombosis, yttrium-90 therapy demonstrated a median overall survival of 13 months and a time to progression of 9 months, indicating its potential efficacy.

The therapy was generally safe, with only 13% of patients experiencing significant hepatobiliary toxicity and no serious complications like radiation pneumonitis or procedure-related mortality, suggesting it is a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label prospective study of the safety and efficacy of glass-based yttrium 90 radioembolization for infiltrative hepatocellular carcinoma with portal vein thrombosis. Kokabi, N., Camacho, JC., Xing, M., et al.[2022]

In a study of 105 patients with hepatocellular carcinoma (HCC) who underwent Yttrium-90 (Y90) radiation segmentectomy, specific tumour dose thresholds were identified that significantly predicted objective tumour response, with a maximum dose of 748 Gy and a mean dose of 568 Gy being particularly notable.

Patients receiving a mean tumour dose of at least 250 Gy had a median overall survival of 43.67 months, compared to 17.87 months for those receiving lower doses, indicating that higher doses correlate with improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of tumour dose response threshold and implication on survival in patients with HCC treated with Y90 radiation segmentectomy: a simple semi-quantitative analysis. Cheng, B., Sethi, I., Villalobos, A., et al.[2023]

Selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 (Y-90) microspheres has been shown to improve survival times in patients with unresectable liver tumors, with responders having a mean overall survival of 25.63 months compared to 20.45 months for non-responders.

The use of F18-FDG PET/CT imaging effectively evaluated treatment response, indicating that a significant decrease in SUV values can predict better survival outcomes, highlighting its role in monitoring therapy effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for unresectable primary and metastatic liver tumors. Kucuk, ON., Soydal, C., Lacin, S., et al.[2022]

Selective internal radiotherapy (SIRT) using yttrium-90 microspheres can enhance clinical outcomes for patients with inoperable liver cancer by targeting tumors while protecting healthy tissue.

Effective planning for SIRT is crucial to avoid serious side effects like radiation-induced liver disease, and it is recommended to use multiple planning methods to determine the appropriate microsphere activity for each patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Lau, WY., Kennedy, AS., Kim, YH., et al.[2022]

A systematic review of 37 studies on selective internal radiation therapy (SIRT) for liver cancer indicates that a higher mean dose threshold (100-250 Gy) is needed for effective treatment of hepatocellular carcinoma (HCC) compared to colorectal cancer metastases (40-60 Gy).

The review highlights the variability in dose-response relationships based on the type of microspheres used, with resin microspheres generally requiring lower doses than glass microspheres, emphasizing the need for standardized reporting and further research to clarify these thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer. Roosen, J., Klaassen, NJM., Westlund Gotby, LEL., et al.[2022]

A 54-year-old woman with multifocal hepatocellular carcinoma showed a dramatic clinical and radiological response after receiving selective internal radiation therapy (SIRT) with yttrium-90 microspheres, 9 weeks post-treatment.

This case highlights the potential effectiveness of SIRT as a treatment option for patients with hepatocellular carcinoma, especially after previous treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dramatic response to selective internal radiation therapy for unresectable hepatocellular carcinoma. Park, WD., Li, BT., Maher, R., et al.[2020]

Selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres shows promise as a treatment option for patients with intermediate and late-stage hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), where traditional treatments may be limited.

Current literature indicates that SIRT is effective in targeting liver tumors while minimizing damage to surrounding healthy tissue, highlighting its potential safety and efficacy in managing these challenging cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma. Wang, EA., Broadwell, SR., Bellavia, RJ., et al.[2020]

In a study of 27 patients with unresectable hepatocellular carcinoma (HCC) treated with yttrium-90 selective internal radiation therapy (90Y-SIRT), the treatment was well-tolerated with no Grade 3-4 clinical toxicities reported, although 38% experienced significant laboratory toxicities within 3 months.

Patients with higher pretreatment bilirubin or transaminase levels were found to be at increased risk for worsening liver function after treatment, indicating the need for careful monitoring in these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma. Gabrielson, A., Miller, A., Banovac, F., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12460054

Stereotactic body radiotherapy with CyberKnife for liver ... The pooled 3-year LC and OS rates were 82.5% (95% confidence interval [CI], 75.0%–90.0%) and 58.7% (95% CI, 47.2%–70.1%), respectively, which is ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7340168/

Long term outcomes of Stereotactic Body Radiation Therapy ... SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard local/regional ...

3. redjournal.org redjournal.org/article/S0360-3016(24)03562-4/fulltext

Final Results of a Multicenter Prospective Study ... Overall, 34 patients were analyzed for efficacy evaluation after excluding 2 patients. The median tumor size was 2.3 cm. The median follow-up ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001551

Long-term outcomes of more than a decade treating ... SBRT resulted in a 5-year LC of 95% in the treatment of primary liver cancer (HCC). •. No SBRT related ≥ grade 3 toxicity was reported. •. Treatment outcomes of ...

5. redjournal.org redjournal.org/article/S0360-3016(23)07777-5/fulltext

Stereotactic Body Radiation Therapy for Hepatocellular ... This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9956001/

Stereotactic Body Radiotherapy for Hepatocellular ... Stereotactic body radiotherapy (SBRT), a type of external beam radiotherapy, yields local control of hepatocellular carcinoma (HCC) at rates as high as 90%.

7. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(23)00241-8/fulltext

Therapeutic Outcome of Stereotactic Body Radiotherapy ... SBRT had significantly less incidence of severe complications compared with surgical resection (odds ratio 0.62, 95% confidence interval 0.42– ...