Ignite Creation Date:
2024-05-06 @ 7:55 PM
Last Modification Date:
2024-10-26 @ 3:16 PM
Study NCT ID:
NCT06182306
Status:
RECRUITING
Last Update Posted:
2024-04-03
First Post:
2023-12-08
Brief Title:
Prospective Evaluation of AI RD Tool for Patient Stratification - MoA Evaluation in Triple Negative Breast Cancer PEAR-MET
Sponsor:
Ourotech Inc
Organization:
Ourotech Inc
Study Overview
Official Title:
Prospective Evaluation of AI RD Tool for Patient Stratification - Mechanism of Action Evaluation in Triple Negative Breast Cancer PEAR-MET
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PEAR-MET
Brief Summary:
Pear Bio has developed an organ-on-a-chip device together with a computer vision pipeline through which the response of an individual patients tumor to different systemic therapy regimens can be tested simultaneously ex vivo This study will recruit patients with advanced or metastatic triple negative breast cancer who are due to start a clinically-indicated new line of therapy
The oncologist will be blinded to the response on the Pear Bio tool the assay will be run in parallel with the patients treatment The primary objective of this study is to establish the sensitivity and specificity of Pear Bios test against patient outcomes response progression-free survival overall survival
The oncologist will be blinded to the response on the Pear Bio tool the assay will be run in parallel with the patients treatment The primary objective of this study is to establish the sensitivity and specificity of Pear Bios test against patient outcomes response progression-free survival overall survival
Detailed Description:
This is a UK-based observational study that aims to discover novel predictive biomarkers with the potential to guide treatment decision making and prolong PFS and OS in patients with advanced TNBC Patients will undergo a mandatory study-specific core needle biopsy or fine needle aspiration of the breast tumour or metastasis before commencing their next line of therapy The research sample will be run on Pear Bios test whilst the patient receives therapy as per their physicians choice This study will not use Pear Bios tool to inform the choice of treatment with the treating oncologist being blinded to the test results Treatment response data will be collected at multiple timepoints to conduct analyses on the studys secondary and tertiary objectives
Fresh tissue resections that arrive at Pear Bios lab will undergo processing cell culture and various drug dosing and omics assays depending on extracted cell numbers Tumour samples will be processed using a cell isolation kit to retrieve a viable single-cell suspension A minimum of 100000 cells 10000 viable cells per chip will be used for staining with live and dead cell-tracking dyes In parallel blood vials will be processed for PBMCs and further effector cell extraction flow cytometry Dynabeads etc The remaining cells will be used for sequencing DNARNA fixed for immunofluorescence characterisation of biomarkersreceptor status or used for further omics assays if cell numbers allow This may include tumour mutational burden and microsatellite instability testing
The stained cells will be cultured in a biomimetic hydrogel within Pear Bios organ-on-a-chip to provide a physiological 3D environment for drug dosing experiments Using a microfluidic device samples in each chip will be exposed to approved therapies either as monotherapy or combination therapies as outlined below over multiple days
In parallel PBMCs will be extracted from whole blood characterised and sorted via flow cytometry and fluorescence-activated cell sorting FACS or magnetic beads selection Cells of interest eg CD8 T cells will be used for culture in Pear Bios chips jointly with cells isolated from the matched tumour sample To test immunotherapies tumour cells will be co-cultured with immune cells in a modified organ-on-a-chip architecture Chips receiving immunotherapies may be tested for tumour mutational burden andor microsatellite instability
Confocal microscopy will be conducted daily to collect 3D image data of the cells and track their position and behaviour over time At the end of the assay the 3D cell cultures will be fixed for further 3D immunofluorescence analyses or used for embedding sectioning and assessment of spatial transcriptomics For targeted therapies RNAseq IF and other omics data will be integrated to confirm drug MoA and identify other potential therapeutic targets Concurrently 3D image data is processed through a computer vision pipeline to measure functional metrics of the ex vivo 3D cell cultures including cell viability cell culture width and cell migration both at a bulk tumour level and at a single-cell resolution For immunotherapies additional metrics such as immune cell infiltration and immune cell killing will be recorded A patient report is then generated to outline an individual patient samples response to each therapy tested
Fresh tissue resections that arrive at Pear Bios lab will undergo processing cell culture and various drug dosing and omics assays depending on extracted cell numbers Tumour samples will be processed using a cell isolation kit to retrieve a viable single-cell suspension A minimum of 100000 cells 10000 viable cells per chip will be used for staining with live and dead cell-tracking dyes In parallel blood vials will be processed for PBMCs and further effector cell extraction flow cytometry Dynabeads etc The remaining cells will be used for sequencing DNARNA fixed for immunofluorescence characterisation of biomarkersreceptor status or used for further omics assays if cell numbers allow This may include tumour mutational burden and microsatellite instability testing
The stained cells will be cultured in a biomimetic hydrogel within Pear Bios organ-on-a-chip to provide a physiological 3D environment for drug dosing experiments Using a microfluidic device samples in each chip will be exposed to approved therapies either as monotherapy or combination therapies as outlined below over multiple days
In parallel PBMCs will be extracted from whole blood characterised and sorted via flow cytometry and fluorescence-activated cell sorting FACS or magnetic beads selection Cells of interest eg CD8 T cells will be used for culture in Pear Bios chips jointly with cells isolated from the matched tumour sample To test immunotherapies tumour cells will be co-cultured with immune cells in a modified organ-on-a-chip architecture Chips receiving immunotherapies may be tested for tumour mutational burden andor microsatellite instability
Confocal microscopy will be conducted daily to collect 3D image data of the cells and track their position and behaviour over time At the end of the assay the 3D cell cultures will be fixed for further 3D immunofluorescence analyses or used for embedding sectioning and assessment of spatial transcriptomics For targeted therapies RNAseq IF and other omics data will be integrated to confirm drug MoA and identify other potential therapeutic targets Concurrently 3D image data is processed through a computer vision pipeline to measure functional metrics of the ex vivo 3D cell cultures including cell viability cell culture width and cell migration both at a bulk tumour level and at a single-cell resolution For immunotherapies additional metrics such as immune cell infiltration and immune cell killing will be recorded A patient report is then generated to outline an individual patient samples response to each therapy tested
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None