Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)

NCT06150898 | Recruiting Phase 2 DMC

• 1 other identifier: IJB-KEPREST-2022
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Early-stage Breast Cancer; Estrogen-receptor-positive Breast Cancer

Keywords

Surgery; Inflammation; Breast cancer; Neuronal features; Ketorolac; Pregabalin; Adiposity; Neurotransmitter; Nerves

Outcome Measures

Primary Outcomes (9)

• To 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

  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)

  Up to 24 hours after surgery

• Change in biomarkers of metastasis at surgery from baseline

  Transcriptome profile and bioinformatic analysis

  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

  At surgery

• Change in tumoral neurogenesis at surgery from baseline

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

  At surgery

• Change in tumoral neurotransmitters level at surgery from baseline

  Using RNA sequencing analysis from fresh frozen tissue sections

  At surgery

• Change in Peripheral Blood Mononuclear Cells at surgery from baseline

  Fluorescence activated cell sorting (FACS) analysis

  At surgery

• Change in systemic neuro-inflammatory mediators at surgery from baseline

  Plasma multiplex technology using cytometric bead arrays

  At surgery

• Change in systemic neurotransmitters at surgery from baseline

  Plasma multiplex technology using cytometric bead arrays

  At surgery

Secondary Outcomes (2)

• Change in anxiety level at surgery from baseline

  At surgery

• Post-operative pain

  Up to 48 hours after surgery

Other Outcomes (3)

• Body Mass Index

  The day before surgery

• Body composition

  The day before surgery

• Waist-to-hip ratio

  The day before surgery

Study Arms (4)

No pre-operative treatment

EXPERIMENTAL

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 )

Procedure: Prospective data and sample collection; Drug: Omeprazole 20mg Capsule

Pre-operative ketorolac

EXPERIMENTAL

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 )

Procedure: Prospective data and sample collection; Drug: Ketorolac 10 Mg Oral Tablet; Drug: Omeprazole 20mg Capsule

Pre-operative pregabalin

EXPERIMENTAL

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 )

Procedure: Prospective data and sample collection; Drug: Pregabalin 75mg; Drug: Omeprazole 20mg Capsule

Pre-operative ketorolac and pregabalin

EXPERIMENTAL

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 )

Procedure: Prospective data and sample collection; Drug: Ketorolac 10 Mg Oral Tablet; Drug: Pregabalin 75mg; Drug: Omeprazole 20mg Capsule

Interventions

Prospective data and sample collection PROCEDURE

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

No pre-operative treatment; Pre-operative ketorolac; Pre-operative ketorolac and pregabalin; Pre-operative pregabalin

Ketorolac 10 Mg Oral Tablet DRUG

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

Pre-operative ketorolac; Pre-operative ketorolac and pregabalin

Pregabalin 75mg DRUG

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

Pre-operative ketorolac and pregabalin; Pre-operative pregabalin

Omeprazole 20mg Capsule DRUG

Patients will receive 20 mg of omeprazole once a day on an empty stomach, for five days before the surgery

Also known as: Auxiliary medicinal product

No pre-operative treatment; Pre-operative ketorolac; Pre-operative ketorolac and pregabalin; Pre-operative pregabalin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria in order to be eligible for this study:
• Age ≥ 18 years and ≤ 70 years old
• Female
• 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 diagnostic ultrasound or MRI/CT scan.
• Stage I, II or III disease (non-metastatic)
• 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
• Subject is willing to provide plasma/blood and tumour samples for translational research.
• 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
• Subject is willing to take omeprazole and has no contraindication to omeprazole.
• Have an HEMSTOP score\<2 and conventional coagulation screening test within normal limits such as activated partial thromboplastin time (21.6\< aPTT \>28.7), international normalised ratio (1.31\<INR) and platelet count (\>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 for women of childbearing potential (within 30 days before start of treatment)

You may not qualify if:

• Subjects meeting one of the following criteria are not eligible for this study:
• Subject planned for intraoperative radiotherapy
• Subject planned for immediate reconstruction
• Neoadjuvant BC therapy
• Allergy to any NSAID or gabapentinoïd
• Known hypersensitivity reactions to the investigational treatments, or any excipients or auxiliary medicinal products or concomitant medications. Hypersensitive to peanut or soya (related to propofol contraindications)
• Current use of the antidiabetic agent thiazolidinedione (related to interaction with pregabalin), lithium salts, probenecid, pentoxifylline or intensive diuretic therapy.
• Current NSAID (\> twice a week the year prior to diagnosis) or pregabalin use
• Active or history of peptic ulcer disease or gastro-intestinal bleeding or perforation
• Pregnancy or lactating women
• Complete or partial nasal polyposis syndrome, Quincke's oedema, bronchospasm, asthma
• Known 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)
• Uncontrolled HIV infection (defined as detectable viral loads by standard clinical assays) or controlled HIV infection (defined undetectable HIV viral loads by standard clinical assays) treated by one of following drugs: Nelfinavir, Atazanavir or Saquinavir (related to interaction with omeprazole).
• Infection currently treated with one of the following drugs: posaconazole, voriconazole, ketoconazole and rifampicin, unless discontinuation of treatment is planned at least 10 days prior to the start of study treatment AND with complete resolution according to expert opinion (related to interaction with omeprazole)
• Inadequate liver function (defined as total serum bilirubin ≥ 2 x upper limit of normal (ULN\<1.2 mg/dl) - unless documented Gilbert syndrome- AND Alanine Aminotransferase (ALT) ≥ 2 x ULN (ULN \<32 UI/l and ULN \<33 UI/l, respectively) AND Alkaline phosphatase (ALP) ≥ 2.5 x ULN (ULN=104 UI/l))

Sponsors & Collaborators

• Jules Bordet Institute: lead
• KU Leuven: collaborator

Study Sites (1)

Institut Jules Bordet

Brussels, Brussels Capital, 1170, Belgium

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Inflammation; Obesity

Interventions

Specimen Handling; Ketorolac; Tablets; Pregabalin; Omeprazole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles

Study Officials

• Christine Desmedt, PhD

  KU Leuven

  STUDY CHAIR

• Imane Bachir, MD

  Jules Bordet Institute

  STUDY CHAIR

Central Study Contacts

Imane Bachir, MD

CONTACT

+3225413601; imane.bachir@bordet.be

Marion Maetens, PhD

CONTACT

+3216321194; marion.maetens@kuleuven.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: November 29, 2023
• Study Start: May 12, 2025
• Primary Completion (Estimated): April 20, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: June 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)