Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Immunomodulating Agents

Patients with advanced or metastatic triple negative breast cancer, due to start a new line of systemic therapy (targeted drug or immunotherapy)

Patients undergo a biopsy from a lesion, and give 40ml of blood

Biopsy

Duleek Ranatunga

Elli Tham

Susan Cleator

Peter Hall, MD PhD

Sheeba Irshad, MD PhD

Pear Bio has developed an organ-on-a-chip device together with a computer vision pipeline through which the response of an individual patient's 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 patient's treatment). The primary objective of this study is to establish the sensitivity and specificity of Pear Bio's test against patient outcomes (response, progression-free survival, overall survival)

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 Bio's test whilst the patient receives therapy as per their physician's choice. This study will not use Pear Bio's 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 study's secondary and tertiary objectives.

Fresh tissue resections that arrive at Pear Bio's 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 100,000 cells (10,000 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 (DNA/RNA), fixed for immunofluorescence characterisation of biomarkers/receptor 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 Bio's 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 (e.g. CD8+ T cells) will be used for culture in Pear Bio's 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 and/or 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 sample's response to each therapy tested.

Prospective Evaluation of AI R&D Tool for Patient Stratification - MoA Evaluation in Triple Negative Breast Cancer (PEAR-MET)

Prospective Evaluation of AI R&D Tool for Patient Stratification - Mechanism of Action Evaluation in Triple Negative Breast Cancer (PEAR-MET)

Pseudonymised data will be shared between study sites, such as treatment and outcome data for each patient. No publication will be made revealing individual patient data; only group-level data will be published.

The percentage of patient samples successfully arriving at central lab with \>100k live cells isolated and maintaining 70% cell viability after 4 days in culture with no treatment

The relationship between DNA, RNA and protein levels and patient outcomes

To conduct dose-response analysis for each commonly used FDA approved therapy, or combination of therapies, to establish the correct dose in the Pear Bio system

The performance (sensitivity, specificity, PPV and NPV) of Pear image-based biomarkers are established against patients' overall response rate (ORR) as defined by RECIST 1.1 guidelines

The performance of Pear image-based biomarkers are established against patients' progression-free survival at 6, 12 and 24 months (evaluated by imaging).

The performance of Pear image-based biomarkers are established against patients' overall survival at 6, 12 and 24 months (evaluated by imaging).

Guys' and St. Thomas Hospital

Barts & The London NHS Trust

Imperial College Healthcare NHS Trust

Nottingham University Hospitals Trust

Hampshire Hospitals NHS Foundation Trust

Ourotech, Inc.

Symptoms and General Pathology

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Micronutrients

Deferasirox

Iron

Chelating Agents

Iron Chelating Agents

All patients are already on commercial deferasirox before entering the study.

Patients experiencing a hematological response and patients not experiencing a hematological response while on deferasirox treatment received a new bone marrow aspirate in order to investigate the presence of differential gene expression between those two groups

Bone marrow aspirate

Patients are already on commercial deferasirox before entering the study.

Several previous studies (clinical and non-clinical) hypothesize that treatment with deferasirox causes a hematological improvement in transfused patients with low and intermediate-1 risk myelodysplastic syndrome. The purpose of this study was to assess the presence of genetic biomarkers predictive for hematologic response by the use of gene expression profiling of bone marrow aspirates obtained from MDS patients with or without hematological response.

This trial was terminated due to low enrollment.

A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy.

A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy in Hematological Centers in Belgium Using Gene Expressing Profiling From Baseline Bone Marrow.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Using next-generation sequencing, gene expression profiling in responder and non-responder patients were to be performed on existing bone marrow aspirate samples. Gene transcription were then to be compared between the two groups and the fold increase/decrease in differentially expressed genes were to be calculated.

The time to response is defined as the time (in months) between the date of deferasirox initiation and the date of the first documented hematological response only in the responder group.

From baseline to time of response (responder group) or time to last follow up (non-responders)

Deferasirox dose is defined as the average daily dose (mg/kg/d) given to the patient from treatment initiation to the emergence of hematological response in the responder group or the time of enrollment in the study in the non-responder group.

Novartis Pharmaceuticals

There was no treatment administration specific to this study. The trial was terminated due to low enrollment. The patient did not experience any Adverse Events during the trial.

Age, Customized

Sex/Gender, Customized

Due to low recruitment (1 patient after 12 months of recruitment) the study has been cancelled. Because there was only 1 patient who enrolled, it's best that the baseline characteristics of this patient be kept confidential, respecting the privacy of this patient.

The trial was terminated due to low enrollment.

Study Director

There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.

Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'

Time to Response

Changes in Serum Ferritin Levels

Deferasirox Dose Used

Changes in Serum Transferrin Levels

Changes in Transferrin Saturation Levels

Overall Study

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

NGS, IHC, methylome and other molecular studies

NGS analysis, other molecular analyses on FFPE tumor tissue

Biomolecular tumor analysis

Q. Giorgio D'Alessandris, MD

Silvia Chiesa, MD

The study envisages NGS analysis on tumor tissue from patients treated with regorafenib for recurrent glioblastoma as per standard care, with the aim to identify predictive biomarkers for response.

Biomolecular Analysis for Predicting Response to Regorafenib

Tumor Biomolecular Analysis for Defining Predictive Factors for Response to Regorafenib in Recurrent Glioblastoma

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Early TNBC patients receiving neoadjuvant therapy and providing core needle biopsy.

Any approved neoadjuvant therapy can be used based on physician's choice.

Early TNBC patients receiving neoadjuvant therapy and providing core needle biopsy and blood.

Any approved neoadjuvant therapy can be used based on physician's choice.

An additional core needle biopsy is taken to run the Pear Bio test. Test results are not used to inform treatment. Approved neoadjuvant therapy regimens are given to the patient as per standard of care to observe response.

Core needle biopsy

Anjali Sivajothi

Peter Hall

Holly Hogan

Charlotte Wood

Pear Bio has developed an organ-on-a-chip device together with a computer vision pipeline through which the response of an individual patient's tumor to different chemotherapy regimens can be tested simultaneously ex vivo. This study will recruit patients with early TNBC who are planned for standard of care neoadjuvant chemotherapy followed by surgery. The oncologist will be blinded to the response on the Pear Bio tool (the assay will be run in parallel with the patient's neoadjuvant chemotherapy). The primary objective of this study is to establish the sensitivity and specificity of Pear Bio's test against patient outcomes (pathological complete response).

This is a multicenter, UK-based, observational pilot study that aims to determine the accuracy of a new assay, the Pear Bio tool, in predicting pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy for early TNBC. Patients will undergo an additional, mandatory biopsy of the breast tumor before commencing neoadjuvant chemotherapy. The biopsy sample will be run on the Pear Bio tool while the patient receives their standard of care neoadjuvant chemotherapy. As such, for this study, the result from the Pear Bio tool will not be used to inform the choice of neoadjuvant chemotherapy and the treating oncologist will be blinded to the assay results. The pathological outcome from surgery (pCR vs non-pCR) will be collected and used to calculate the specificity of the assay as the primary endpoint of the study. Sensitivity, positive predictive value and negative predictive value will also be measured.

Image-based AI Predictive Biomarkers for Precision Neoadjuvant Triple-negative Breast Cancer Treatment

Prospective Evaluation of Image-based Artificial Intelligence Research and Development Tool for Precision Neoadjuvant Triple-Negative Breast Cancer Treatment

Pseudonymized data will be shared between study sites, such as treatment and outcome data for each patient. No publication will be made revealing individual patient data; only group-level data will be published.

The specificity of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

The sensitivity of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

The positive predictive value of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

The negative predictive value of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

Mouth and Tooth Diseases

Head and Neck Neoplasms

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Cancer

Lip and Oral Cavity Cancer

Histologically diagnosed cases of head and neck cancer

Next generation Sequencing

Manoj Pandey, MS, PhD

Keshav Murthy, MS

Based on the recently identified mutations in HNSCCs, the major pathologic pathways implicated in the tumorigenesis of HNSCC include dysregulation of four processes:

1. cellular survival and proliferation (e.g., TP53, EGFR, MET, and PIK3CA);
2. cell-cycle control (e.g., CDKN2A and CCND1);
3. cellular differentiation (e.g., NOTCH1); and
4. Adhesion and invasion signaling (e.g., FAT1).7 TP53, EGFR, PIK3CA, CDKN2A, CCND1, and MET participate in several common signaling pathways.

Alterations of these genes are most frequently seen in alcohol and tobacco-related HNSCC. However their role in prognostication and selection of therapeutics is not known

Sample size:

Patients with squamous cell carcinoma of oral cavity fulfilling the inclusion and exclusion criteria and willing to participate will be included in this study.

Method:

Comprehensive history and physical examination of the patients will be carried out and all the details will be recorded in the preset proforma. All routine investigations as indicated including a biopsy to establish a diagnosis and CT of the head and neck to measure the tumor dimensions and stage the disease before initiation of treatment will be recorded. The paraffin embedded tissue will be studied for expression of various genetic mutations using NGS platform. Brush cytology will be collected in liquid medium for HPV typing using PCR.

The Ion AmpliSeq™ Cancer Hotspot Panel v3 will be used to detect hotspot regions of 161 oncogenes and tumor suppressor genes This research panel, with improved primer design, contains 4,648 total 4 pools (DNA pool 1: 1,891 amplicons. DNA pool 2: 1,890 amplicons. RNA pool 1: 447 amplicons. RNA pool 2: 420 amplicons.), enabling researchers to sequence challenging samples of formalin-fixed, paraffin-embedded (FFPE) tissue. Copy Number Variants (CNVs), Gene Fusions, Insertions-Deletions (indels), Single Nucleotide Polymorphisms (SNPs), Somatic Variants are identified.

HPV DNA PCR METHODOLOGY

DNA will be isolated by using QIAamp DNA mini kit (Qiagen, Hilden, Germany). The presence of HPV will be detected by using the digene® HC2 HPV DNA Test- The digene HC2 HPV DNA Test uses Hybrid Capture 2 technology to detect high-risk and low-risk HPV genotypes. It uses in vitro microplate assay based on signal-amplified nucleic acid hybridization that uses chemiluminescence for the qualitative detection of 18 types of human papillomavirus (HPV) (13 high risk and 5 low risk) DNA in cervical specimens. The test uses an RNA probe cocktail that detects 13 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/68) and 5 low-risk types (6/11/42/43/44).

Newer Therapeutic Targets in Head and Neck Cancers

A Cohort Study to Identify Newer Therapeutic Targets in Head and Neck Cancers

Survival time from the diagnosis to death

survival time from diagnosis to recurrence or metastasis

The time from the diagnosis to progression of disease

Banaras Hindu University

Professor

Nervous System Diseases

Brain Neoplasms

Ependymoma

Oligodendroglioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Patients with a solid primary brain tumor due to undergo surgery as standard of care

Patients undergo a resection from a lesion, and give 40mL of blood

Resection

Waqar Saleem, MRCP FRCR

Matt Williams, FRCR PhD

Pear Bio has developed a 3D microtumor assay and computer vision pipeline through which the response of an individual patient's tumor to different anti-cancer regimens can be tested simultaneously ex vivo. This study will recruit patients with primary brain tumors who are due to undergo surgery.

Oncologists will be blinded to treatment response on the Pear Bio tool (the assay will be run in parallel with the patient's treatment). The primary objective of this study is to establish the ex vivo model and confirm whether approved therapies exhibit their intended mechanism of action in the model. Secondary objectives include correlating test results to patient outcomes, where available.

This is a multicenter, observational pilot study that aims to determine the feasibility of using the Pear Bio tool in patients with primary solid brain tumors.

Patients who are due to undergo clinically-mandated surgery will provide informed consent to donate excess tissue and a 40mL blood sample.

The samples will be tested on the Pear Bio tool while the patient receives their standard of care treatment. As such, for this study, the result from the Pear Bio tool will not be used to inform the choice of treatment and the treating oncologist will be blinded to the assay results.

The investigators will examine drug mechanism of action (MoA), differentiated response, and correlate that with outcomes seen in the patients treated in routine clinical practice.

Prospective Evaluation of AI R&D Tool in Adult Glioma and Other Primary Brain Tumours (PEAR-GLIO)

The percentage of cultures in which ≥70% of viable tumor cells encapsulated post-isolation on day 0 are still alive on day 3 in the control cultures (no treatment) compared to the number of tumor samples successfully accepted at the study central lab.

The percentage of cultures in which ≥70% of viable immune cells plated post-extraction on day 0 are still alive on day 3 in the control cultures (no treatment) compared to the number of blood samples successfully accepted at the study central lab.

To correlate Pear assay results, biomarkers and outcomes

Categorisation of patients into survival cohorts using the Pear assay

Correlation between biomarkers and clinically relevant outcomes

Measurement of treatment response in the Pear Assay

The correlation between response in the Pear Bio system and PFS in patients

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Tumor molecular profiling

Elena Fountzila

We aim to employ targeted DNA NGS to evaluate the prevalence of germline and somatic mutations in cancer predisposing genes, such as BRCA1 and BRCA2, and other HR and DDR genes, including also a few additional clinically relevant genes, in patients with metastatic, locally advanced or high-grade prostate cancer. In addition, we will investigate the prognostic role of these mutations as well as their association with various clinicopathological parameters. This will be the first study investigating the prevalence of germline and somatic pathogenic mutations in Greek patients with prostate cancer.

This study will include formalin-fixed paraffin-embedded tumor tissue (FFPE) from 250 patients with metastatic, recurrent, locally advanced or "intermediate or high risk" (Gleason \>7), operable prostate cancer. FFPE tumor blocks alongside peripheral blood will be retrieved for all patients from Pathology Laboratories. Available FFPE blocks will be subjected to histological review by an experienced pathologist to evaluate H\&E sections for confirmation of diagnosis, histologic type, grade and tumor cell content (TCC%), as well as mark tumor dense areas for manual macro-dissection, prior to DNA extraction, in order to enrich samples for tumor DNA. Clinicopathologic characteristics of patients with prostate cancer will be retrieved from their respective medical records. Diagnosis will be confirmed through pathology reports, which will also provide information about Gleason Score and histological subtype.

In all instances, the collection of patient information will be in compliance with the regulations of the Bioethics committees of participating Hospitals. The study will be conducted in accordance with the principles of the Helsinki Declaration of Human Rights.

Following manual macro-dissection, FFPE tumor tissue material will be processed for DNA extraction, according to standard procedures with the QIAamp DNA Mini Kit (Qiagen GmbH, Hilden, Germany).

Sequencing will be performed at the Laboratory of Molecular Oncology, using an Ion Torrent Proton Sequencer (Life Technologies/Ion Torrent). For the purpose of targeted NGS genotyping of tumor and available matched germline DNA samples, we designed a custom Ampliseq panel to target coding relevant regions of genes involved in homologous recombination (HR), along with several others.

Data retrieval and base calling will be performed on the Torrent Server (v5.8.0.8). Consequently, we will then employ appropriate Ion Reporter Workflows (version 5.10) to automatically annotate single nucleotide variants (SNVs), multiple nucleotide variants (MNVs), small insertions / deletions (INDELs) and copy number variations (CNVs).

Formalin-fixed paraffin-embedded tissue samples and germline DNA

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Evaluation of AI R&D Tool for Patient Stratification - MoA Evaluation in Triple Negative Breast Cancer (PEAR-MET)	NCT06182306	Breast Cancer Triple Negative...	Biopsy	18 Years -	Ourotech, Inc.
A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy.	NCT02663752	Myelodysplastic...	Bone marrow asp... Deferasirox	18 Years -	Novartis
Biomolecular Analysis for Predicting Response to Regorafenib	NCT05759195	Glioblastoma Glioblastoma, I...	Biomolecular tu...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Image-based AI Predictive Biomarkers for Precision Neoadjuvant Triple-negative Breast Cancer Treatment	NCT05435352	Triple Negative... Triple Negative...	Core needle bio...	18 Years -	Ourotech, Inc.
Newer Therapeutic Targets in Head and Neck Cancers	NCT05382585	Head Neck Cance... Oral Cancer	Next generation...	18 Years - 100 Years	Banaras Hindu University
Prospective Evaluation of AI R&D Tool in Adult Glioma and Other Primary Brain Tumours (PEAR-GLIO)	NCT06038760	Brain Tumor Glioma, Maligna... Ependymoma Oligodendroglio... Glioblastoma	Resection	18 Years -	Ourotech, Inc.
Molecular Profiling in Prostate Cancer	NCT04983628	Prostate Cancer... Prostate Cancer... Germline BRCA1 ... Germline BRCA2 ... Mutation	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Peritoneal Surface Malignancies - Characterization, Models and Treatment Strategies	NCT02073500	Pseudomyxoma Pe... Colorectal Carc... Ovarian Carcino... Mesothelioma	Observational s...	18 Years -	Oslo University Hospital
Breathomics as Predictive Biomarker for Checkpoint Inhibitor Response	NCT04146064	NSCLC Melanoma Kidney Cancer Urothelial Carc... Head and Neck C...	Breathprint ana...	18 Years -	University Health Network, Toronto
Biomolecular Analysis for Predicting Response to Regorafenib	NCT05759195	Glioblastoma Glioblastoma, I...	Biomolecular tu...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Spots Global Cancer Trial Database for predictive biomarker