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

Inflammation

Channel Blockers

Analgesics

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Bone Density Conservation Agents

Pregabalin

Ketorolac

Ketorolac Tromethamine

Calcium

Calcium Channel Blockers

Calcium, Dietary

Hormones

Anti-Anxiety Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Control group: Standard of care

Number of subjects: 28 (14 lean patients, defined as Body mass index \<25 kg/m², and 14 overweight/obese patients, defined as BMI ≥25 kg/m² )

Investigational Medicinal Product (IMP): Ketorolac

Number of subjects: 28 (14 lean patients, defined as Body mass index \<25 kg/m², and 14 overweight/obese patients, defined as BMI ≥25 kg/m² )

Investigational Medicinal Product (IMP): Pregabalin

Number of subjects: 28 (14 lean patients, defined as Body mass index \<25 kg/m², and 14 overweight/obese patients, defined as BMI ≥25 kg/m² )

Investigational Medicinal Products (IMPs): Ketorolac and pregabalin

Number of subjects: 28 (14 lean patients, defined as Body mass index \<25 kg/m², and 14 overweight/obese patients, defined as BMI ≥25 kg/m² )

Core-needle biopsy of the breast (pre-treatment), surgical sample collection (post-treatment), extra collection of blood samples (pre- and post-treatment), measurements of adiposity

Patients will receive 10 mg film-coated tablets of ketorolac tromethamine three times a day, for five days before the surgery

Ketorolac 10 Mg Oral Tablet

Patients will receive 75 mg of pregabalin hard capsule twice a day, for seven days before the surgery

Pregabalin 75mg

Imane Bachir, MD

Maher Khalife, MD

Laurence Buisseret, MD, Phd

Isabelle Veys, MD

Elia Biganzoli, PhD

Juan A Rodriguez Arango, MD

Denis Larsimont, MD, PhD

Out of all proportion to its short duration, the perioperative period is critical in determining the long-term outcome of cancer.

To contribute to a better understanding of the neural and inflammatory mechanisms underlying this issue, we aim to implement a novel intervention based on the preoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) with or without an anti-epileptic drug.

Our goal is to understand and transform the perioperative window from being a facilitator of metastatic progression to arresting and/or eliminating residual disease using repurposing drugs

The perioperative period presents a unique window of therapeutic opportunities to counteract minimal residual growth and dormancy escape of cancer cells. The main physiological disturbances induced by the surgery, that enhance the tumoral growth in the perioperative period, are due to the neuronal and inflammatory signaling.

We propose a therapeutic modelling of the inflammatory and neurological pathways in a phase II trial using ketorolac and pregabalin, alone or in combination. Ketorolac, a non-selective NSAIDs will target cyclooxygenase (COX)-enzymes, while pregabalin, an anti-epileptic drug will regulates the release of neurotransmitters. Moreover, both drugs have an effect on the postoperative pain and pregabalin has anxiolytic property. Thanks to this study, and through specific blockade, we want to understand how nervous and inflammatory systems remodel the tumour and systemic characteristics. To ensure an integrative analysis of those factors, patient's adiposity as well as other confounding variable will be taken into account.

Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)

Unravelling the Local and Systemic Effects of Primary Surgery and Perioperative Use of Ketorolac and Pregabalin in Primary Breast Cancer Patients According to Adiposity

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

Plasma multiplex technology using cytometric bead arrays

Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)

Transcriptome profile and bioinformatic analysis

Characterization of Tumour-infiltrating leukocyte subpopulations using RNA sequencing analysis from fresh frozen tissue sections

Level of neurogenesis markers using RNA sequencing analysis from fresh frozen tissue section

Using RNA sequencing analysis from fresh frozen tissue sections

Fluorescence activated cell sorting (FACS) analysis

Generalized Anxiety Disorder - 7 (GAD - 7) Anxiety score (natural number, range\[0 - 21\]. A score comprised between 0 - 4 indicates a minimal anxiety, 5-9 a mild anxiety, 10-14 a moderate anxiety and a 15-21 in a severe anxiety.

Consumption of morphine delivered by a programmable patient-controlled analgesia (PCA) infusion pump (number of requested and effectively delivered bolus/ 24h)

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
Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)	NCT06150898	Early-stage Bre... Estrogen-recept...	Prospective dat... Ketorolac 10 Mg... Pregabalin 75mg	18 Years - 70 Years	Jules Bordet Institute
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
Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)	NCT06150898	Early-stage Bre... Estrogen-recept...	Prospective dat... Ketorolac 10 Mg... Pregabalin 75mg	18 Years - 70 Years	Jules Bordet Institute

Spots Global Cancer Trial Database for prospective data and sample collection