Nutritional and Metabolic Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Obesity

Breast Neoplasms

Inflammatory Breast Neoplasms

Breast Diseases

Skin Diseases

Overweight

Overnutrition

Nutrition Disorders

Body Weight

Inflammatory Breast Cancer

Performance of measurements of adiposity, extra collection of blood samples

Prospective data and sample collection

Marion Maetens, PhD

Tatjana Geukens, MD

Christine Desmedt, PhD

Giuseppe Floris, MD PhD

FATLAS is a prospective, interventional, non Investigational Medicinal Product (IMP) study aiming to characterize the micro- and macroenvironment of breast cancer according to patient adiposity in different histological and molecular subtypes.

The macroscopic profiling of the patient's adiposity will be based on Body Mass Index (BMI), bioimpedance analysis and waist-to-hip ratio. Blood samples will be taken for lipidomic analyses and for hormonal and immuno assays. Microscopic profiling of adiposity and inflammation will be done on fresh frozen (FF) and Formalin-Fixed Paraffin-Embedded (FFPE) samples from the tumour resection specimen and will consist of histological characterization, immuno assays, multiplex immunohistochemistry, DNA sequencing and single nuclei RNA sequencing both in the tumour and in adjacent normal mammary tissue.

FATLAS: Comprehensive Multi-level Characterization of Systemic and Mammary Adiposity in Breast Cancer Patients.

Calculated: body mass (kg) divided by height squared (m²)

Single nucleus RNA sequencing using 10X Genomics Platform after dissociation of tissue into single nuclei

Number of T-cells per population using immunohistochemical phenotypic markers of cell type and of exhaustion.

Time of activity of different intensities and time of sedentarity, evaluated using the Global Physical Activity Questionnaire (GPAQ) of the World Health Organisation (WHO) (scale: minutes per day, range \[0 - 1440\]). The higher the score for activity the better, the lower the score for sedentarity the better.

Pittsburgh Sleep Quality Index (PSQI) score (range: \[0 - 21\]). Higher scores indicate worse sleep quality.

Nutritional score (natural number, range \[0 - 100\]) calculated using the in-house Food Frequency Questionnaire. A score of \> 70 indicates healthy dietary behaviour.

Food intake in kcal per day calculated using the in-house Food Frequency Questionnaire.

Calculated from multiple frequency bio-impedance measurements (in %, range \[0 - 100\]).

Waist circumference (cm) divided by hip circumference (cm)

In kilograms (kg), measured by handheld dynamometer.

KU Leuven

Universitaire Ziekenhuizen KU Leuven

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Immunomodulating Agents

Pierce Chow, MD, PhD

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world but the 2nd most important cause of cancer death. Because of its highly heterogeneous nature, the current approach to identifying druggable targets have not delivered efficacious therapies in HCC and is a main reason for the high case fatality. Even when surgical resection is potentially curative in early disease, tumor recurrence remains high and long term survival poor because of the absence of useful adjuvant therapy.

To address these unmet needs, the investigators bring together internationally recognized scientists from genomics and immunology and established clinician investigators in a synergistic team. This TCR capitalizes on recent collaborative advances made by the PIs in the consortium. The investigators have shown through multi-region sampling of freshly resected HCC and phylogenetic analysis, that significant intra-tumoral heterogeneity exists and have identified the specific positions of known clonal drivers. Simultaneously the investigators have analyzed the immune landscape of the tumor microenvironment with deep immune-phenotyping and found unique inter-patient immune landscapes predictive of clinical trajectory.

This TCR is a prospective study that samples resected HCC from multi-ethnic sites within the established Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group, which has enrolled approximately 1000 patients through 6 multi-center trials in 35 centers in the region. Clinical trajectories are tracked and genomic and immunological studies are repeated when tumors recu r, to confirm clonally dominant driver mutations and immunological processes that are targetable. Concurrently, representative pre-clinical models will be developed from the tissues sampled.

The investigators aim to combine these approaches to overcome the challenges posed by genomic heterogeneity and to guide the development of therapeutics and precision medicine in HCC.

Tumour samples Blood samples Urine samples

Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma

A Multi-National Cohort Study On The Impact Of Intra-Tumoural Genomic Heterogeneity And The Immune Micro-Environment On The Clinical Trajectory Of Resected Hepatocellular Carcinoma

Singapore Clinical Research Institute

National Cancer Centre, Singapore

Immune System Diseases

Blood and Lymph Conditions

Melanoma

Head and Neck Neoplasms

Sarcoma

Hypersensitivity

Lymphoma

Soft Tissue Sarcoma

Lymphosarcoma

Antineoplastic Agents

Pharmaceutical Solutions

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients with HNSCC who are scheduled for surgical biopsy or tumour resection surgery will be injected at least four hours to up to three days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline and solution stabilizer), a pre-cleaved/pre-activated drug control (cMVC-101), MVC-101 (the prodrug), or nivolumab as single agents or as combinations. Each drug will be delivered in subtherapeutic microdoses, and each microdose is simultaneously injected in a columnar fashion through each of 3, 5, or 8 needles (in a device configuration determined by tumour dimensions) into a single solid tumour or effaced metastatic lymph node.

Intratumoural microdose injection by the CIVO device.

MVC-101

MVC-101 + Nivolumab

Medical Director

This is a multi-center, open-label Phase 0 Master Protocol in Australia designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the tumour microenvironment (TME) when administered intratumourally in microdose quantities via the CIVO device in patients with surface accessible solid tumours for which there is a scheduled surgical intervention. CIVO stands for Comparative In Vivo Oncology. Multiple substudies will include specified investigational agents and combinations to be evaluated.

CIVO is a research tool composed of a hand-held single-use sterile injector coupled with fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose injection, enabling rapid assessment of multiple oncology drugs or drug combinations simultaneously within a patient's tumour. Tumour responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumour cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoural microdose injections with CIVO in advance of scheduled surgical intervention, this study will evaluate anti-cancer therapies directly in patients each with their own unique tumour genomic profile, intact TME, and immune system functional status. Because the platform delivers microdose amounts of each test agent or combination directly into the patient's tumour tissue, hypotheses can be tested earlier in the drug development process.

The CIVO device penetrates solid tumours and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumour as drug columns. At the time of the planned surgical intervention (at least four hours to up to seven days after the CIVO microdose injection), the injected tumour tissue is then excised and tumour responses are assessed via histological staining of tumour cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. This Phase 0 Master Protocol is aimed at distinguishing promising candidates earlier in the drug development process while also avoiding systemic toxicities associated with typical clinical exposures to these therapies.

This Master Protocol is designed as an umbrella concept trial for the ongoing evaluation of multiple agents in individual CIVO Phase 0 substudies. Each substudy is considered an "Experimental Arm" with specified investigational agents and combinations to be evaluated. Comparisons will not be made between experimental arms.

CIVO Intratumoural Microdosing of Anti-Cancer Therapies in Australia

A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoural Microdoses of Anti-Cancer Therapies in Patients With Solid Tumours

Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumour microenvironment around each of the injection sites in each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumour response. The biomarkers evaluated may include, but are not limited to biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B, CD4), natural killer (NK)/myeloid cells (e.g. CD56/Granzyme B, CD86, CD68, CD163), and proinflammatory cytokines (e.g., interferon gamma, tumour necrosis factor alpha, interferon gamma-induced protein 10).

Relationship of AE to study drug(s) or CIVO device will be determined using an AE Relatedness Grading System.

Takeda

Presage Biosciences

Colorectal Neoplasms

Colonic Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Anti-Infective Agents

Herbal and Botanical

Formaldehyde

Cola

Immunoscore® is a tissue-based immune test that measures the host's immune response at the site of the tumor. It is performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from resections of localized colon cancer. The test uses whole slide imaging and artificial intelligence algorithms for assessment of the type, density, and location of T cells in FFPE tumor sections to determine an individual Immunoscore® for each patient.

Immunoscore Colon Test

Camila M Moniz, PhD

Ingrid P Barbosa

Lucila S Rocha, MD

Mariana B Siqueira, MD

Paulo M Hoff, PhD

Fernando A Soares, PhD

The proposed study is a bidirectional analytical study, composed of a retrospective and a prospective cohorts. Patients with stage II - III colorectal cancer undergoing oncological surgery will be analyzed. The study will include a convenience sample of 100 individuals. Fifty cases will be included retrospectively and fifty prospectively.

The study aims to evaluate the benefit of using the Immunoscore test as a predictor of recurrence in patients with operated stage II-III colon tumors. It will also be evaluated the impact on oncologic decision and costs.

Colorectal cancer resection surgical biospecimen

Role of Immunoscore® in Stage II-III Colorectal Cancer

Impact of Immunoscore stratification on tumor recurrence at 2 years

Impact of Immunoscore stratification on DFS at 5 years

Impact of Immunoscore stratification on OS at 5 years

Impact of Immunoscore stratification on DFS in right and left tumors at 3 years

Impact of Immunoscore stratification on OS in right and left tumors at 3 years

Percentage of patients who had an indication for adjuvant therapy through the evaluation of medical prescriptions

Correlation of Immunoscore stratification with the KRAS, NRAS and BRAF status

Difference in monetary value due to Immuno Score stratification and chemotherapy indication

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FATLAS: Comprehensive Multi-level Characterization of Systemic and Mammary Adiposity in Breast Cancer Patients.	NCT04200768	Breast Neoplasm...	Prospective dat...	18 Years - 75 Years	Universitaire Ziekenhuizen KU Leuven
FATLAS: Comprehensive Multi-level Characterization of Systemic and Mammary Adiposity in Breast Cancer Patients.	NCT04200768	Breast Neoplasm...	Prospective dat...	18 Years - 75 Years	Universitaire Ziekenhuizen KU Leuven
FATLAS: Comprehensive Multi-level Characterization of Systemic and Mammary Adiposity in Breast Cancer Patients.	NCT04200768	Breast Neoplasm...	Prospective dat...	18 Years - 75 Years	Universitaire Ziekenhuizen KU Leuven
Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma	NCT03267641	Hepatocellular ...		21 Years - 80 Years	National Cancer Centre, Singapore
CIVO Intratumoural Microdosing of Anti-Cancer Therapies in Australia	NCT04891718	Solid Tumour	MVC-101 Nivolumab MVC-101 + Nivol...	18 Years -	Presage Biosciences
Role of Immunoscore® in Stage II-III Colorectal Cancer	NCT05422547	Colon Adenocarc...	Immunoscore Col...	-	D'Or Institute for Research and Education

Spots Global Cancer Trial Database for tumour microenvironment