Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jules Bordet Institute
• Collaborators: KU Leuven; University of Milan
• Treatments: Ketorolac; Pregabalin

Criteria

Inclusion Criteria:

• Weight ≥ 35 kg

• Histological diagnosis of invasive breast adenocarcinoma that is estrogen receptor-positive as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing with ER-positive is defined as having an immunohistochemistry (IHC) of 1% or more and/or Allred score of 3 or more

• Tumour size ≥ 1.5 cm, determined by imaging.

• N0 or N1

• In case of multifocal, multicentric unilateral or bilateral breast: Adenocarcinoma tumours are allowed provided that all foci are ER+ according to local testing

• Subject scheduled for a primary breast cancer surgery at the Institut Jules Bordet

• Subject is willing to provide plasma/blood and tumour samples for translational research.

• If not available yet, subject is willing to provide tissue from a newly obtained core or excisional biopsy of the tumour that should be evaluable for central histological characterization and future molecular testing

• Have an HEMSTOP score<2 (see appendix "2. HEMSTOP score") and conventional coagulation screening test within normal limits such as activated partial thromboplastin time (21.6< aPTT >28.7), international normalised ratio (1.31(>100.10³/ml)

• Women of childbearing potential must agree to use of one highly effective method of contraception prior study entry, during the course of the study and at least one months after the last administration of study treatment.

• Negative serum pregnancy test

• Completion of all necessary screening procedures prior to randomisation

• Subject is willing and able to provide written informed consent for the trial

Exclusion Criteria:

• Subject planned for intraoperative radiotherapy

• Subject planned for immediate reconstruction

• Neoadjuvant BC therapy

• Allergy to NSAID or gabapentinoïd

• Hypersensitive to peanut or soya (related to propofol contraindications)

• Current use of the antidiabetic agent thiazolidinedione (related to interaction with pregabalin)

• Current NSAID (> twice a week the year prior to diagnosis) or pregabalin use

• Previous malignant pathology within 5 years prior to inclusion. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that have undergone potentially curative therapy or in situ cervical cancer.

• Active or history of peptic ulcer disease or gastro-intestinal bleeding or perforation

• Pregnancy or lactating women

• Chronic inflammatory disease as rheumatoid arthritis, uncontrolled asthma, chronic heart failure, chronic obstructive pulmonary disease , cystic fibrosis, inflammatory myopathies (e.g., idiopathic polymyositis, dermatomyositis, inclusion body myositis), inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), McArdle's disease, multiple sclerosis , lupus, chronic inflammatory demyelinating polyneuropathy, psoriasis, autoimmune thyroiditis as Graves' disease or Hashimoto's thyroiditis (unless previous surgical ablation), myasthenia gravis, vasculitis

• Chronic infectious disease as active hepatitis B (defined as positive serology for Ac anti-HBc and IgM anti HBc OR Ac anti HBc and Ag HBs), active hepatitis C (defined as positive serology for anti-VHC and positive PCR-VHC) or active tuberculosis (included under treatment)

• Inadequate liver function (defined as total serum bilirubin ≥ 2 x upper limit of normal (ULN) - unless documented Gilbert syndrome- AND Aspartate and Alanine Aminotransferase (AST and ALT) ≥ 2 x ULN AND Alkaline phosphatase ≥ 2.5 x ULN)

• Renal impairment (defined as GFR<90ml/min/1.73m²) or single kidney or previous renal surgery 15) Cardiovascular disease (defined as history of ischemic heart disease or heart failure or uncontrolled high blood pressure-Systolic≥160mmHg and/or diastolic≥100mmHg- or peripheral arterial disease or cerebrovascular disease) 16) Hemostasis disorder as haemophilia, Von Willebrand disease, constitutional thrombopathies or thrombocytopenia (defined as platelet count < 100 000/mm³), current /planned anticoagulant or anti-platelet therapy.

• Inadequate bone marrow function (defined as absolute neutrophil count <1000/μL and platelet count <100'000/μL)

• Systemic immunosuppressive treatment (defined as systemic corticotherapy or anti-rejection treatment or interferon therapy) within the 2-years prior diagnosis

• Psychiatric disease or antipsychotic/ antidepressant use

• Epilepsy or any current anti-epileptic drug use

• Obstructive sleep apnea

• ASA≥3