Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)

Trial Title: Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)

NCT ID: NCT06150898

Condition: Early-stage Breast Cancer
Estrogen-receptor-positive Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Ketorolac
Pregabalin

Conditions: Keywords:
Surgery
Inflammation
Breast cancer
Neuronal features
Ketorolac
Pregabalin
Adiposity
Neurotransmitter
Nerves

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Other

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: Prospective data and sample collection
Description: 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
Arm group label: No pre-operative treatment
Arm group label: Pre-operative ketorolac
Arm group label: Pre-operative ketorolac and pregabalin
Arm group label: Pre-operative pregabalin

Intervention type: Drug
Intervention name: Ketorolac 10 Mg Oral Tablet
Description: Patients will receive 10 mg film-coated tablets of ketorolac tromethamine three times a day, for five days before the surgery
Arm group label: Pre-operative ketorolac
Arm group label: Pre-operative ketorolac and pregabalin

Intervention type: Drug
Intervention name: Pregabalin 75mg
Description: Patients will receive 75 mg of pregabalin hard capsule twice a day, for seven days before the surgery
Arm group label: Pre-operative ketorolac and pregabalin
Arm group label: Pre-operative pregabalin

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

Detailed description: 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.

Criteria for eligibility:
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 (1.31100.10³/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

Gender: Female

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: Imane Bachir

Address:
City: Brussels
Zip: 1170
Country: Belgium

Contact:
Last name: Imane Bachir, MD

Phone: +3225413601
Email: imane.bachir@hubruxelles.be

Contact backup:
Last name: Maher Khalife, MD

Phone: +325413368
Email: maher.khalife@hubruxelles.be

Investigator:
Last name: Maher Khalife, MD
Email: Principal Investigator

Investigator:
Last name: Imane Bachir, MD
Email: Sub-Investigator

Investigator:
Last name: Laurence Buisseret, MD, Phd
Email: Sub-Investigator

Investigator:
Last name: Isabelle Veys, MD
Email: Sub-Investigator

Investigator:
Last name: Elia Biganzoli, PhD
Email: Sub-Investigator

Investigator:
Last name: Juan A Rodriguez Arango, MD
Email: Sub-Investigator

Investigator:
Last name: Denis Larsimont, MD, PhD
Email: Sub-Investigator

Start date: February 20, 2024

Completion date: December 2026

Lead sponsor:
Agency: Jules Bordet Institute
Agency class: Other

Collaborator:
Agency: KU Leuven
Agency class: Other

Collaborator:
Agency: University of Milan
Agency class: Other

Source: Jules Bordet Institute

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06150898