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

Brown University1 site in 1 country18 target enrollmentApril 7, 2025

ConditionsColorectal Carcinoma Metastatic in the Liver

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Colorectal Carcinoma Metastatic in the Liver
Sponsor: Brown University
Enrollment: 18
Locations: 1
Primary Endpoint: 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
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 7, 2025

End Date

September 1, 2029

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Brown University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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

Exclusion Criteria

•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

Outcomes

Primary Outcomes

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

Time Frame: 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).

Secondary Outcomes

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)