Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 7:14 PM
Ignite Modification Date:
2025-12-24 @ 7:14 PM
NCT ID:
NCT03307603
Brief Summary:
This study has two portions. The main goal of the Phase Ib portion of this research study is to see at what time Yttrium-90 (Y-90) radioembolization therapy and nivolumab can safely be given to patients without having too many side effects. Other purposes of this research study will be to study any tumor responses.
The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment. The study team will pick the part of the study each subject participates in.
Y-90 radioembolization therapy is minimally invasive procedure that combines two types of therapy (embolization which blocks certain blood vessels, and radiation therapy, which kills cancer cells) to treat cancer tumors in the liver. This works with tiny glass or resin beads filled with the radioactive isotope yttrium-90 (Y-90). They are placed inside the blood vessels that feed the tumor in the liver. This blocks the supply of blood to the cancer cells and delivers a high dose of radiation to the tumor while sparing normal tissue.
Nivolumab is an FDA approved medicine that is used for the treatment of different types of cancers and metastases (second growths from cancer).
Detailed Description:
Primary Objective
Phase Ib: To determine the safety and tolerability of Y-90 radioembolization therapy when given in conjunction with neoadjuvant/adjuvant nivolumab as assessed by CTCAE version 4, in patients with metastatic colorectal cancer who undergo Y-90 radioembolization to hepatic metastases and have additional disease located outside of the radioembolization field.
Phase II: To determine the objective response rate (RR) as assessed by RECIST criteria of metastases located outside of the Y-90 radioembolization treatment field in patients with metastatic colorectal cancer who undergo Y-90 radioembolization to hepatic metastases and receive neoadjuvant/adjuvant nivolumab.
Secondary Objectives
Phase Ib:
To assess the response rate (RR) of patients with metastatic colorectal cancer who undergo standard Y-90 radioembolization therapy to hepatic metastases as well as neoadjuvant/adjuvant nivolumab as assessed by measurement of foci located outside of the Y-90 radioembolization field.
Phase II:
To assess the progression free survival (PFS) of patients with metastatic colorectal cancer who undergo standard Y-90 radioembolization therapy to hepatic metastases as well as neoadjuvant/adjuvant nivolumab as assessed by measurement of metastatic foci located outside of the Y-90 radioembolization field.
To assess the 1-year and 2-year overall survival (OS) rate of patients with metastatic colorectal cancer who undergo standard Y-90 radioembolization therapy to hepatic metastases as well as neoadjuvant/adjuvant nivolumab.
Correlative Objectives
To characterize the baseline expression and localization of immune markers including Programmed cell death protein 1 (PD-1), Programmed cell death protein ligand 1 (PD-L1), Programmed cell death protein ligand 2 (PD-L2), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), Lymphocyte activation gene 3 (LAG-3), Tumor necrosis factor receptor superfamily, member 4 (OX40) and Cluster of Differentiation 137 (CD137) within the tumor microenvironment and correlate this with treatment response.
To examine the change in density of Cluster of Differentiation (CD8)+/Kiel-67 (Ki-67) high tumor infiltrating lymphocytes and expression levels of PD-L1 in the tumor parenchyma prior to and following treatment with Y-90 and nivolumab as assessed in a lesion outside of the radioembolization field. Changes in biomarkers will be correlated with treatment response.
To assess baseline and changes in the immune signature of Y-90 naïve colorectal cancer in patients with liver metastases who receive Y-90 radioembolization and nivolumab therapy. Human transcriptome gene expression arrays will be performed and expression data will be used to identify immune cell subsets using CIBERSORT and immune signatures will be assessed using ImmuneSigDB.
To assess baseline and changes in non-targeted tumor antigens using Proto Array Human Protein MicroArray Profiling and Immunoglobulin G (IgG) quantification in patients with liver metastases who receive Y-90 radioembolization and nivolumab therapy. Changes in profile will be correlated with treatment response.
Study Design
This is a single arm phase Ib/II trial assessing the safety and toxicity (phase Ib) followed by the antitumor activity (response rate) (phase II) of nivolumab when administered in combination with Y-90 radioembolization therapy.
Study design
Eligible patients will undergo Y-90 radioembolization to one side of the liver according to standard practice as directed by an interventional radiologist. Yttrium-90 will be given as biocompatible resin-based microspheres and will be introduced to the tumor(s) on one side of the liver through a catheter placed in the right or left hepatic artery (depending on the lobe treated). The dose of radiation will be determined by a radiologist and will be based on body surface area and tumor burden. During the phase Ib portion of the study, nivolumab will be administered per the scheduling algorithm at a flat dose of 240 mg intravenously over 30 +/- 5 minutes. Depending on the schedule being assessed, this may include a neoadjuvant dose to be given prior to Y-90, and will contain an adjuvant dose following Y-90 therapy. During the phase II portion of the study, nivolumab will be administered as determined during the phase Ib portion of the study. Nivolumab will continue to be administered on an every 2 week basis for a total of 48 weeks or until disease progression, unacceptable toxicity or discontinuation due to patient/physician preference. Patients will be evaluated with a history and physical exam as well as laboratory parameters once every 2 weeks throughout the duration of the study. Patients will undergo CT scans of the chest and pelvis as well as MRI of the liver to assess disease status 2 months following the Y-90 radioembolization procedure, then every 3 months for a total of 2 years. Upon completing treatment, patients will be followed monthly for another 100 days for toxicity monitoring. Archived tissue specimens will be obtained at baseline and a post-treatment biopsy of a metastatic lesion located outside of the Y-90 radioembolization field will be obtained 60 +/- 5 days following treatment with Y-90 radioembolization for assessment of intratumoral immunogenicity. Carcinoembryonic antigen (CEA) levels will be assessed at baseline, then once monthly for 6 months, then every 3 months for a total of 2 years. Patients will have a pre-treatment serum sample collected as well as post-treatment samples collected approximately 6 weeks, 12 weeks and 20 weeks after treatment with Y-90 radioembolization for banking, to be used in the future assessment of putative biomarkers.
Study:
NCT03307603
Study Brief:
Protocol Section:
NCT03307603