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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
112
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, lifestyle questionaire
Patients will receive 10 mg film-coated tablets of ketorolac tromethamine three times a day, for five days before the surgery
Patients will receive 75 mg of pregabalin hard capsule twice a day, for seven days before the surgery
Patients will receive 20 mg of omeprazole once a day on an empty stomach, for five days before the surgery
Institut Jules Bordet
Brussels, Brussels Capital, Belgium
RECRUITINGTo detect a reduced increase in systemic inflammation (from baseline to up to 24 hours after surgery) using peri-operative ketorolac
Plasma multiplex technology using cytometric bead arrays
Time frame: Up to 24 hours after surgery
To detect a reduced increase in systemic neurotransmitters (from baseline to up to 24 hours after surgery) using peri-operative pregabalin
Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS)
Time frame: Up to 24 hours after surgery
Change in biomarkers of metastasis at surgery from baseline
Transcriptome profile and bioinformatic analysis
Time frame: At surgery
Change in tumoral immune cells recruitment at surgery from baseline
Characterization of Tumour-infiltrating leukocyte subpopulations using RNA sequencing analysis from fresh frozen tissue sections
Time frame: At surgery
Change in tumoral neurogenesis at surgery from baseline
Level of neurogenesis markers using RNA sequencing analysis from fresh frozen tissue section
Time frame: At surgery
Change in tumoral neurotransmitters level at surgery from baseline
Using RNA sequencing analysis from fresh frozen tissue sections
Time frame: At surgery
Change in Peripheral Blood Mononuclear Cells at surgery from baseline
Fluorescence activated cell sorting (FACS) analysis
Time frame: At surgery
Change in systemic neuro-inflammatory mediators at surgery from baseline
Plasma multiplex technology using cytometric bead arrays
Time frame: At surgery
Change in systemic neurotransmitters at surgery from baseline
Plasma multiplex technology using cytometric bead arrays
Time frame: At surgery
Change in anxiety level at surgery from baseline
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.
Time frame: At surgery
Post-operative pain
Consumption of morphine delivered by a programmable patient-controlled analgesia (PCA) infusion pump (number of requested and effectively delivered bolus/ 24h)
Time frame: Up to 48 hours after surgery
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