Y-90 + Capecitabine + Atezolizumab for Colorectal Cancer

(METEORITE Trial)

Overseen By Brown University Oncology Research Group (BrUOG)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brown University

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Autoimmune disease, Heart failure, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: 93

Duration: 12 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with colorectal cancer that has spread to the liver and cannot be surgically removed. It combines internal radiation therapy (yttrium-90), a chemotherapy drug (capecitabine), and an immunotherapy drug (atezolizumab) to evaluate their combined effectiveness. The trial seeks participants who have undergone colorectal cancer treatment at least twice but still have cancer primarily in the liver that has not responded to those treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that you stop any systemic treatments at least 14 days or 5 half-lives of the drug (whichever is longer) before starting the study treatment. If you are on systemic immunosuppressive medication, you must stop it 2 weeks before starting the trial, unless it's a low-dose or specific type allowed by the study.

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

Research shows that the combination of Y-90 (a type of radiation therapy), capecitabine (a chemotherapy drug), and atezolizumab (an immune therapy) is generally well-tolerated. Studies have found that Y-90 and capecitabine can be used together safely without major safety concerns at the doses tested. This combination treats colorectal cancer that has spread to the liver, especially after other treatments have been tried. Overall, previous research indicates that the treatment's safety is acceptable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Y-90, capecitabine, and atezolizumab for colorectal cancer because it brings together innovative approaches that may enhance treatment effectiveness. Unlike standard chemotherapy, Y-90 uses radioembolization to deliver radiation directly to tumors in the liver, potentially increasing precision and minimizing damage to surrounding healthy tissue. Capecitabine, an oral chemotherapy, works alongside Y-90, while atezolizumab, an immunotherapy, helps the immune system recognize and attack cancer cells. This multi-pronged approach could offer improved outcomes compared to traditional treatments like surgery and systemic chemotherapy.

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

This trial will evaluate the combination of yttrium-90 (Y-90) radioembolization, capecitabine, and atezolizumab for colorectal cancer that has spread to the liver. Studies have shown that Y-90 can effectively treat liver metastases from colorectal cancer, significantly decreasing tumor size and improving survival rates for some patients. Capecitabine, a chemotherapy drug, enhances the effects of radiation treatments like Y-90. Atezolizumab, an immunotherapy drug, enables the immune system to find and attack cancer cells. Combining these treatments might increase their effectiveness in managing liver cancer that cannot be surgically removed. Early results are promising, but more research is needed to confirm these findings. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with colorectal cancer that has spread to the liver and can't be removed by surgery. Participants must have tried at least two systemic therapies without success, be in good physical condition (ECOG 0 or 1), and willing to provide tissue and blood samples. They should also have adequate kidney, liver, and blood function.

Inclusion Criteria

My liver function tests are within the required limits.

My blood counts meet the required levels for treatment.

My diagnosis is colorectal adenocarcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive yttrium-90 radioembolization in combination with capecitabine and atezolizumab for the treatment of unresectable colorectal cancer liver metastases

12 weeks

Atezolizumab IV every 3 weeks for 5 doses, Capecitabine PO BID for 2 weeks per Y-90 therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 18 months

CT imaging every 90 days (+14 days) until disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Y-90

Trial Overview The study tests a combination of Y-90 radioembolization with capecitabine chemotherapy and Atezolizumab immunotherapy on patients with advanced colorectal cancer in the liver. It's a phase 2 trial where all participants receive this same treatment regimen.

How Is the Trial Designed?

Group I: yttriuM-90 in combination with capEcitabine and aTezolizumab Experimental Treatment 1 Intervention

Atezolizumab 1,200 mg IV every 3 weeks for 5 doses Capecitabine 825 mg/m2 PO BID for 2 weeks beginning on the date of each Y-90 therapy administration Y-90 radioembolization one or both hemilivers based on distribution of disease

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Sirtex Medical

Industry Sponsor

Trials

30

Recruited

4,300+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

Atezolizumab monotherapy demonstrated a manageable safety profile in Chinese patients with previously treated advanced non-small cell lung cancer (NSCLC), with serious adverse events occurring in 25.7% of patients and immune-related adverse events in 47.5%.

The treatment showed clinically meaningful efficacy, with a median overall survival of 15.31 months and a 24-month overall survival rate of 37.4%, while specific gene mutations and the presence of CD8+ TILs were associated with better responses to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of atezolizumab in Chinese patients with previously treated locally advanced or metastatic non-small cell lung cancer: An open-label, single-arm, multicenter study. Xu, Y., Huang, Z., Chang, J., et al.[2023]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

In a phase 2 study involving 218 patients with previously untreated metastatic colorectal cancer, the addition of atezolizumab to the standard chemotherapy regimen (FOLFOXIRI plus bevacizumab) significantly improved median progression-free survival to 13.1 months compared to 11.5 months in the control group.

The treatment was found to be safe, with the most common serious side effects being neutropenia and diarrhoea, although there were two treatment-related deaths in the atezolizumab group, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. Antoniotti, C., Rossini, D., Pietrantonio, F., et al.[2022]

A phase III study found that the combination of atezolizumab and cobimetinib did not show improved effectiveness compared to standard therapy (regorafenib) in patients with inoperable, locally advanced, or metastatic colorectal cancer.

The overall survival for patients receiving the combination treatment was 8.9 months, slightly higher than the 8.5 months for those on standard therapy, but the response rates were very similar at 2.7% for the combination versus 2.2% for regorafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Duo Disappoints in Colorectal Cancer. [2019]

In a phase Ib study involving 20 patients with platinum-resistant ovarian cancer, the combination of atezolizumab and bevacizumab demonstrated a safety profile consistent with the individual drugs, with 95% experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment resulted in a 15% overall response rate, with some patients achieving durable responses lasting up to 18.9 months, and a disease control rate of 55%, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. Moroney, JW., Powderly, J., Lieu, CH., et al.[2021]

Atezolizumab, a PD-L1 inhibitor, was well tolerated in patients with advanced ovarian and uterine cancers, with no new safety concerns and mostly mild treatment-related adverse events.

Preliminary results showed anti-tumor activity in some patients, with long durations of response, suggesting that atezolizumab may be a promising treatment option for these cancers, especially in those with high microsatellite instability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. Liu, JF., Gordon, M., Veneris, J., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4110696/

Yttrium-90 Radioembolization of Hepatic Metastases from ... Surgical resection of liver metastases provides the best 5-year survival, in the order of 40%, and is possible if the disease is localized or downgraded with ...

2. jvir.org jvir.org/article/S1051-0443(24)00454-8/fulltext

Outcomes Analysis of Yttrium-90 Radioembolization for ... To characterize the response and survival outcomes of yttrium-90 ( 90 Y) transarterial radioembolization (TARE) for unresectable, liver-dominant metastases.

3. clinical-colorectal-cancer.com clinical-colorectal-cancer.com/article/S1533-0028(22)00100-1/fulltext

Results From the Multicentre Observational Study CIRT Transarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.4_suppl.686

Molecular profiling to predict outcomes following Y90 ... The purpose of this study was to evaluate predictive associations between genetic mutations in Y90 treated CRC pts and treatment outcomes. Methods: A ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S153300282500026X

Escalated Segmental and Modified Radiation Lobectomy ... Y90 TARE with escalated dosing demonstrated an acceptable safety profile in heavily pretreated mCRC patients. Extrahepatic disease and pre-NLR were significant ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06555133

NCT06555133 | Y-90, Capecitabine, and Atezolizumab for ... Study Plan ; To assess the preliminary efficacy with the combination of yttrium-90, capecitabine, and atezolizumab based on the intrahepatic disease control rate ...

7. withpower.com withpower.com/trial/phase-2-colorectal-carcinoma-metastatic-in-the-liver-7-2024-8f9da

Y-90 + Capecitabine + Atezolizumab for Colorectal Cancer The treatment showed clinically meaningful efficacy, with a median overall survival of 15.31 months and a 24-month overall survival rate of 37.4%, while ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8497089/

Radioembolization in the Setting of Systemic Therapies These data suggest that combined Y90 and capecitabine can be administered together without particular safety concerns at the doses described. The SIRFLOX study, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1051044324003981

Multidisciplinary Delphi Consensus on Safety of ... A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies.

10. academicradiology.org academicradiology.org/cms/10.1016/j.acra.2025.01.044/attachment/dc654047-4c90-477f-bfde-011ddc91f6c2/mmc1.docx

Document (108.60 KB) This study cannot obtain data. 2024. A Phase II Pilot Study of yttriuM-90 in Combination With capEcitabine and aTezolizumab for oligomEtastatic cOlorectal ...