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

Trial Summary

What is the purpose of this trial?

BrUOG-430 is a prospective, single-arm, phase 2 trial evaluating yttrium-90 radioembolization in combination with capecitabine and atezolizumab for the treatment of unresectable colorectal cancer liver metastases in individuals who have been treated with two or more lines of systemic therapy.

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 the combination of Y-90, Capecitabine, and Atezolizumab safe for humans?

Atezolizumab has been studied for safety in various cancers, including lung cancer and colorectal cancer, and is generally considered safe, though it can have side effects like fatigue and skin reactions. It is important to discuss potential risks with your doctor, as individual responses can vary. ^{1 2 3 4 5}

What makes the Y-90 + Capecitabine + Atezolizumab treatment unique for colorectal cancer?

This treatment combines Y-90, a type of radiation therapy, with capecitabine, a chemotherapy drug, and atezolizumab, an immune therapy that targets PD-L1 to help the immune system attack cancer cells. This combination is unique because it integrates different approaches to target cancer cells from multiple angles, potentially offering benefits for patients with specific genetic profiles of colorectal cancer. ^{4 5 6 7 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The real-world safety of atezolizumab as second-line or later treatment in Japanese patients with non-small-cell lung cancer: a post-marketing surveillance study. [2023]

2. Ireland 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. [2023]

3. England 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. [2020]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]

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

Drug Duo Disappoints in Colorectal Cancer. [2019]

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

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. [2021]

8. United States 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. [2019]