Y-90, Capecitabine, and Atezolizumab for Oligometastatic CRC

NCT06555133 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: BrUOG 430
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Carcinoma Metastatic in the Liver

Outcome Measures

Primary Outcomes (1)

• To assess the preliminary efficacy with the combination of yttrium-90, capecitabine, and atezolizumab based on the intrahepatic disease control rate (iDCR) at 12 weeks

  Disease control rate is defined as the proportion of patients with complete response (CR), partial response (PR), or stable disease (SD) within the liver at first post-Y-90 follow-up imaging by NCI's response evaluation criteria in solid tumors (RECIST 1.1), which is a standard way to measure if the tumor is responding to treatment by measuring tumor lesions (cm).

  12 weeks

Secondary Outcomes (3)

• To evaluate the preliminary safety of the combination of yttrium-90, capecitabine, and atezolizumab

  Approximately 18 months

• To determine the extrahepatic disease control rate (eDCR) with the combination of yttrium-90, capecitabine, and atezolizumab

  Approximately 18 months

• To estimate the median overall response rate (ORR), progression free survival (PFS), and overall survival (OS) with the combination of yttrium-90, capecitabine, and atezolizumab

  Approximately 18 months

Study Arms (1)

yttriuM-90 in combination with capEcitabine and aTezolizumab

EXPERIMENTAL

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

Combination Product: yttrium-90 radioembolization

Interventions

yttrium-90 radioembolization COMBINATION_PRODUCT

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.

Also known as: capecitabine and atezolizumab

yttriuM-90 in combination with capEcitabine and aTezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of colorectal adenocarcinoma
• Surgically unresectable, liver-isolated or liver-dominant, RECIST measurable, metastatic disease
• Age ≥18 years at the time of signing informed consent
• ECOG performance status 0 or 1
• Progression on 2 or more lines of systemic therapy
• Agreeable to providing tumor tissue and blood for exploratory correlative analyses
• Less than 50% of liver volume replaced by metastatic disease (as determined by investigator)
• Demonstrate adequate organ function as defined in table below (all screening labs should be performed within 14 days of atezolizumab initiation):
• Hematologic Absolute neutrophil count (ANC) ≥1,500 /mcL or ≥1,200 /mcL for those with benign ethnic neutropenia Absolute Lymphocyte Count (ALC) ≥ 0.5 x 109/L (500/uL) Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L within 7 days of assessment. Patient may be transfused or receive EPO to meet this criterion
• Renal Serum creatinine OR measured or calculated creatinine clearance ≤1.5 X upper limit of normal (ULN) OR (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 5 X ULN Alkaline Phosphatase ≤ 5 X ULN Albumin ≥2.5 mg/dL
• Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• ≤1.5 X ULN unless subject is receiving anticoagulant therapy. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Creatinine clearance should be calculated per institutional standard. Exceptions can be made for patients with known Gilbert disease (≤ 3X ULN)
• 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.

You may not qualify if:

• Prior yttrium-90 therapy
• Prior external beam radiation therapy to the liver
• Predicted life expectancy of less than 3 months
• Known mismatch repair deficiency (dMMR), microsatellite instability (MSI-H), or high tumor mutational burden (TMB-H) defined as ≥ 10 mutations per megabase
• 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
• Treatment with investigational therapy within the 28 days of initiation of study treatment
• Systemic treatment within 14 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Prior treatment with CD137 agonists or anti-PD1, anti-PD-L1, anti-CTLA4 antibodies
• 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
• 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
• Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or chronic oxygen
• 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
• 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.

Sponsors & Collaborators

• Brown University: lead
• Sirtex Medical: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

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

Providence, Rhode Island, 02903, United States

RECRUITING

MeSH Terms

Interventions

Capecitabine; atezolizumab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2024
• First Posted: August 15, 2024
• Study Start: April 7, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

US (1)