Combined Y-90 SIRT + SBRT for Liver Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Kyle C. Cuneo

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Michigan Rogel Cancer Center

Disqualifiers: Pregnancy, Allergy to contrast, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study will investigate the combination of Ytrium-90 (Y-90) Selective Internal Radiation Therapy (SIRT) followed by Stereotactic Body Radiation Therapy (SBRT). Y-90 SIRT alone or SBRT alone are standard procedures used in the treatment of liver cancer. This study will assess the combination of Y-90 SIRT and SBRT and obtain preliminary information about the side effects and safety of the combination therapy. Additionally, this is the first time that Y-90 PET-CT imaging will be included in planning for SBRT.

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.

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

Research shows that selective internal radiation therapy (SIRT) with yttrium-90 can improve outcomes for patients with inoperable liver cancer, including hepatocellular carcinoma (HCC). In one case, a patient with HCC experienced a dramatic response to SIRT after other treatments failed, highlighting its potential effectiveness. ^{1 2 3 4 5}

Is the combination of Y-90 SIRT and SBRT safe for liver cancer treatment?

Yttrium-90 selective internal radiation therapy (Y-90 SIRT) has been used safely in treating liver cancers like hepatocellular carcinoma and intrahepatic cholangiocarcinoma, with safety confirmed over two decades of clinical use. It is important to have a multidisciplinary team to manage the treatment and monitor for any adverse reactions or complications. ^{6 7 8 9 10}

What makes the Y-90 SIRT + SBRT treatment for liver cancer unique?

The Y-90 SIRT + SBRT treatment is unique because it combines selective internal radiation therapy (SIRT) with Yttrium-90, which targets liver tumors directly through the bloodstream, with stereotactic body radiation therapy (SBRT), a precise form of external radiation. This combination aims to enhance the effectiveness of treatment by delivering high doses of radiation directly to the tumor while minimizing damage to surrounding healthy tissue. ^{4 5 7 9 11}

Research Team

Kyle C. Cuneo

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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

I am 18 years old or older.

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.

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.

Trial Timeline

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)

Treatment Details

Interventions

• PET/CT (Diagnostic Test)
• Selective Internal Radiation Therapy (Radioisotope Therapy)
• Stereotactic Body Radiation Therapy (Radiation)
• Yttrium-90 (Radioisotope Therapy)

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.

Participant Groups

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

Y-90 SIRT followed by SBRT

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Marschall S. Runge

University of Michigan Rogel Cancer Center

Chief Executive Officer since 2015

MD, PhD

Eric R. Fearon

University of Michigan Rogel Cancer Center

Chief Medical Officer since 2016

MD, PhD

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Dr. Bruce J. Tromberg

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Chief Executive Officer since 2019

PhD in Biomedical Engineering from the University of California, Irvine

Dr. Nina F. Schor

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Chief Medical Officer since 2023

MD from Harvard Medical School

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

Dr. Georges C. Benjamin

Department of Health and Human Services

Chief Medical Officer

MD from Harvard Medical School

Robert F. Kennedy Jr.

Department of Health and Human Services

Chief Executive Officer

JD from University of Virginia School of Law

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Dramatic response to selective internal radiation therapy for unresectable hepatocellular carcinoma. [2020]

4. Germany 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. [2022]

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

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. [2022]

6. China pubmed.ncbi.nlm.nih.gov

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

7. China pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma. [2020]

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

Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma? [2019]

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

Yttrium-90 Radiation Segmentectomy in Oligometastatic Secondary Hepatic Malignancies. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for unresectable primary and metastatic liver tumors. [2022]