RECRUITING

Y-90, Capecitabine, and Atezolizumab for Oligometastatic CRC

Conditions

Colorectal Carcinoma Metastatic in the Liver

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase II Pilot Study of yttriuM-90 in Combination With capEcitabine and aTezolizumab for oligomEtastatic cOlorectal Cancer With unResectable lIver MeTastasEs (METEORITE)

Quick Facts

Study Start:2025-04-07

Study Completion:2029-09-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06555133

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Histologically confirmed diagnosis of colorectal adenocarcinoma 2. Surgically unresectable, liver-isolated or liver-dominant, RECIST measurable, metastatic disease 3. Age ≥18 years at the time of signing informed consent 4. ECOG performance status 0 or 1 5. Progression on 2 or more lines of systemic therapy 6. Agreeable to providing tumor tissue and blood for exploratory correlative analyses 7. Less than 50% of liver volume replaced by metastatic disease (as determined by investigator) 8. Demonstrate adequate organ function as defined in table below (all screening labs should be performed within 14 days of atezolizumab initiation): 9. Female subjects of childbearing potential must be willing to use an adequate method of contraception from the time of the negative pregnancy test until a minimum of 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive (injectable or implantable), or intrauterine device in conjunction with a barrier method. Breast feeding subjects must be willing to discontinue at treatment start and for 5 months post-treatment. 10. Male subjects of childbearing potential must agree to use an adequate method of contraception with female partners of childbearing potential including abstinence or condoms plus an additional contraceptive method such as hormonal contraceptive (injectable or implantable), or intrauterine device during the study and for up to 3 months after the last dose of study drug. 11. Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures	1. Prior yttrium-90 therapy 2. Prior external beam radiation therapy to the liver 3. Predicted life expectancy of less than 3 months 4. Known mismatch repair deficiency (dMMR), microsatellite instability (MSI-H), or high tumor mutational burden (TMB-H) defined as ≥ 10 mutations per megabase 5. Known metastasis to the peritoneum or central nervous system. Exceptions include subjects with untreated brain metastases ≤ 1 cm, if asymptomatic and not requiring immediate radiation or steroids, and subjects with brain metastases that are treated and stable for 1 month 6. Treatment with investigational therapy within the 28 days of initiation of study treatment 7. Systemic treatment within 14 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment 8. Prior treatment with CD137 agonists or anti-PD1, anti-PD-L1, anti-CTLA4 antibodies 9. A history of or current evidence of any condition (e.g. known deficiency of the enzyme dihydropyrimidine dehydrogenase \[DPD\]), therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator 10. Known New York Heart Association class 3/4 congestive heart failure, left ventricular ejection fraction \<40% (if previously measured), myocardial infarction within 6 months prior to enrollment, unstable angina, or unstable arrhythmia 11. Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or chronic oxygen 12. History of autoimmune disease, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the exception of: hypothyroidism (on stable dose of thyroid replacement therapy), asthma managed with inhaled medications only; type 1 diabetes mellitus on stable insulin regimen, Sjögren syndrome, immune thrombocytopenia or autoimmune hemolytic anemia that does not require systemic therapy; dermatologic condition (including eczema, psoriasis, lichen simplex chronicus, or vitiligo) with skin manifestations with rash covering \<10% of body surface area and not requiring treatment other than low-potency topical corticosteroids for \>12 months prior to registration 13. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study. * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. 14. Positive for HIV at screening or any time prior to screening: patients without prior positive HIV test result will undergo an HIV test at screening, unless not permitted under local regulations 15. Active Hepatitis B virus (HBV) infection (chronic or acute): defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody test at screening, are eligible for the study 16. Active hepatitis C virus (HCV) infection: defined as positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test 17. Active TB (Mycobacterium tuberculosis) 18. Administration of a live, attenuated vaccine within 28 days before first atezolizumab dose or anticipation that such a live, attenuated vaccine will be required during the study or within 5 months after the final dose of atezolizumab 19. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation 20. Inability to swallow medication 21. History of other malignancy that could affect compliance with the protocol or interpretation of results; patients with a curatively treated skin cancer, in situ cervical cancer, or non-CRC malignancy are eligible if the non-CRC malignancy is controlled and will not interfere with measurement of treatment efficacy or safety 22. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 28 days before the first dose of atezolizumab. 23. Any major surgery or significant traumatic injury within 28 days of initiating study treatment or anticipation of need for a major surgical procedure during the study 24. Evidence of other significant or uncontrolled medical or psychiatric conditions that could affect compliance with the protocol 25. Pregnancy, breast-feeding, or prisoner status 26. History of leptomeningeal disease 27. Uncontrolled tumor-related pain 28. Patients requiring pain medication must be on a stable regimen at study entry. 29. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. 30. Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12 mg/dL or corrected serum calcium ULN) 31. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. 32. Prior allogeneic stem cell or solid organ transplantation 33. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications 34. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

Inclusion Criteria

Exclusion Criteria

1. Histologically confirmed diagnosis of colorectal adenocarcinoma
2. Surgically unresectable, liver-isolated or liver-dominant, RECIST measurable, metastatic disease
3. Age ≥18 years at the time of signing informed consent
4. ECOG performance status 0 or 1
5. Progression on 2 or more lines of systemic therapy
6. Agreeable to providing tumor tissue and blood for exploratory correlative analyses
7. Less than 50% of liver volume replaced by metastatic disease (as determined by investigator)
8. Demonstrate adequate organ function as defined in table below (all screening labs should be performed within 14 days of atezolizumab initiation):
9. Female subjects of childbearing potential must be willing to use an adequate method of contraception from the time of the negative pregnancy test until a minimum of 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive (injectable or implantable), or intrauterine device in conjunction with a barrier method. Breast feeding subjects must be willing to discontinue at treatment start and for 5 months post-treatment.
10. Male subjects of childbearing potential must agree to use an adequate method of contraception with female partners of childbearing potential including abstinence or condoms plus an additional contraceptive method such as hormonal contraceptive (injectable or implantable), or intrauterine device during the study and for up to 3 months after the last dose of study drug.
11. Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures

1. Prior yttrium-90 therapy
2. Prior external beam radiation therapy to the liver
3. Predicted life expectancy of less than 3 months
4. Known mismatch repair deficiency (dMMR), microsatellite instability (MSI-H), or high tumor mutational burden (TMB-H) defined as ≥ 10 mutations per megabase
5. Known metastasis to the peritoneum or central nervous system. Exceptions include subjects with untreated brain metastases ≤ 1 cm, if asymptomatic and not requiring immediate radiation or steroids, and subjects with brain metastases that are treated and stable for 1 month
6. Treatment with investigational therapy within the 28 days of initiation of study treatment
7. Systemic treatment within 14 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
8. Prior treatment with CD137 agonists or anti-PD1, anti-PD-L1, anti-CTLA4 antibodies
9. A history of or current evidence of any condition (e.g. known deficiency of the enzyme dihydropyrimidine dehydrogenase \[DPD\]), therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
10. Known New York Heart Association class 3/4 congestive heart failure, left ventricular ejection fraction \<40% (if previously measured), myocardial infarction within 6 months prior to enrollment, unstable angina, or unstable arrhythmia
11. Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or chronic oxygen
12. History of autoimmune disease, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the exception of: hypothyroidism (on stable dose of thyroid replacement therapy), asthma managed with inhaled medications only; type 1 diabetes mellitus on stable insulin regimen, Sjögren syndrome, immune thrombocytopenia or autoimmune hemolytic anemia that does not require systemic therapy; dermatologic condition (including eczema, psoriasis, lichen simplex chronicus, or vitiligo) with skin manifestations with rash covering \<10% of body surface area and not requiring treatment other than low-potency topical corticosteroids for \>12 months prior to registration
13. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
* Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
14. Positive for HIV at screening or any time prior to screening: patients without prior positive HIV test result will undergo an HIV test at screening, unless not permitted under local regulations
15. Active Hepatitis B virus (HBV) infection (chronic or acute): defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody test at screening, are eligible for the study
16. Active hepatitis C virus (HCV) infection: defined as positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test
17. Active TB (Mycobacterium tuberculosis)
18. Administration of a live, attenuated vaccine within 28 days before first atezolizumab dose or anticipation that such a live, attenuated vaccine will be required during the study or within 5 months after the final dose of atezolizumab
19. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
20. Inability to swallow medication
21. History of other malignancy that could affect compliance with the protocol or interpretation of results; patients with a curatively treated skin cancer, in situ cervical cancer, or non-CRC malignancy are eligible if the non-CRC malignancy is controlled and will not interfere with measurement of treatment efficacy or safety
22. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 28 days before the first dose of atezolizumab.
23. Any major surgery or significant traumatic injury within 28 days of initiating study treatment or anticipation of need for a major surgical procedure during the study
24. Evidence of other significant or uncontrolled medical or psychiatric conditions that could affect compliance with the protocol
25. Pregnancy, breast-feeding, or prisoner status
26. History of leptomeningeal disease
27. Uncontrolled tumor-related pain
28. Patients requiring pain medication must be on a stable regimen at study entry.
29. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
30. Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12 mg/dL or corrected serum calcium ULN)
31. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
32. Prior allogeneic stem cell or solid organ transplantation
33. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
34. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

Contacts and Locations

Study Contact

Brown University Oncology Research Group (BrUOG)

CONTACT

401-863-3000

BrUOG@brown.edu

Alexander G Raufi, MD

CONTACT

401-787-0988

Alexander_Raufi@brown.edu

Study Locations (Sites)

Lifespan Cancer Institute: The Miriam and Rhode Island Hospitals Providence, Rhode Island, United States, 02903 Contact:

Providence, Rhode Island, 02903

United States

Collaborators and Investigators

Sponsor: Brown University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-07

Study Completion Date2029-09-01

Study Record Updates

Study Start Date2025-04-07

Study Completion Date2029-09-01

Terms related to this study

Additional Relevant MeSH Terms

Colorectal Carcinoma Metastatic in the Liver