Early-stage Breast CancerPhase 2KePreStNCT06150898
Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)
A Phase 2 study testing Prospective data and sample collection, Ketorolac 10 Mg Oral Tablet and Pregabalin 75mg in people with Early-stage Breast Cancer and Estrogen-receptor-positive Breast Cancer, run by Jules Bordet Institute at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Early-stage Breast Cancer, Estrogen-receptor-positive Breast Cancer
- What is being tested?
- Prospective data and sample collection, Ketorolac 10 Mg Oral Tablet and Pregabalin 75mg
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteBelgium
- Study dates
- 12 May 2025to Oct 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
- Subject is willing and able to provide written informed consent for the trial
Who cannot join
- 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)
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- 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
- Previous malignant pathology within 5 years prior to inclusion or currently undergoing maintenance therapy. 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.
- 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))
- Cirrhosis or severe hepatitis.
- Renal impairment (defined as GFR<90ml/min/1.73m² or serum creatinine > 442 μmol/l or > 5 mg/dL) or single kidney or previous renal surgery
- Subject with history of (severe) renal toxicity with an NSAID
- Subject with a recent history of operations associated with a high risk of bleeding
- Previous, ongoing or suspected 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
- Subject with a recent history of surgery associated with a high risk of bleeding
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
Institut Jules Bordet
Brussels, 1170
Imane Bachir, MD, +322541 ext. 3601, imane.bachir@hubruxelles.be
Sophie Vankerkhove, +322541 ext. 7341, sophie.vankerckhove@hubruxelles.be
About this study
Official title: Unravelling the Local and Systemic Effects of Primary Surgery and Perioperative Use of Ketorolac and Pregabalin in Primary Breast Cancer Patients According to Adiposity
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
Read the 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.
- Being tested
- Prospective data and sample collection, Ketorolac 10 Mg Oral Tablet, Pregabalin 75mg, Omeprazole 20mg Capsule
- Keywords
- Surgery, Inflammation, Breast cancer, Neuronal features, Ketorolac, Pregabalin, Adiposity, Neurotransmitter, Nerves
- Medical subject headings
- Breast Neoplasms, Inflammation, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prospective data and sample collectionProcedure or surgery
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
Ketorolac 10 Mg Oral TabletDrug
Patients will receive 10 mg film-coated tablets of ketorolac tromethamine three times a day, for five days before the surgery
Pregabalin 75mgDrug
Patients will receive 75 mg of pregabalin hard capsule twice a day, for seven days before the surgery
Omeprazole 20mg CapsuleDrug
Also called Auxiliary medicinal product
Patients will receive 20 mg of omeprazole once a day on an empty stomach, for five days before the surgery
| Study group | Role | What they receive |
|---|---|---|
| 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 ) Receives: 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 ) Receives: 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 ) Receives: 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 ) Receives: Procedure: Prospective data and sample collection; Drug: Ketorolac 10 Mg Oral Tablet; Drug: Pregabalin 75mg; Drug: Omeprazole 20mg Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: Up to 24 hours after surgery
Change in biomarkers of metastasis at surgery from baseline
Transcriptome profile and bioinformatic analysis
Measured: 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
Measured: At surgery
Change in tumoral neurogenesis at surgery from baseline
Level of neurogenesis markers using RNA sequencing analysis from fresh frozen tissue section
Measured: At surgery
Change in tumoral neurotransmitters level at surgery from baseline
Using RNA sequencing analysis from fresh frozen tissue sections
Measured: At surgery
Change in Peripheral Blood Mononuclear Cells at surgery from baseline
Fluorescence activated cell sorting (FACS) analysis
Measured: At surgery
Change in systemic neuro-inflammatory mediators at surgery from baseline
Plasma multiplex technology using cytometric bead arrays
Measured: At surgery
Change in systemic neurotransmitters at surgery from baseline
Plasma multiplex technology using cytometric bead arrays
Measured: At surgery
Secondary outcomes (2)
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.
Measured: 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)
Measured: Up to 48 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2023
- Study start12 May 2025
- Primary completion20 Apr 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-stage Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jules Bordet Institute
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven
- Responsible party
- Sponsor
- Investigators
- Christine Desmedt, PhD, Study chair, KU LeuvenImane Bachir, MD, Study chair, Jules Bordet Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06150898
- Sponsor's protocol ID
- IJB-KEPREST-2022
- Acronym
- KePreSt
- Status last verified
- Sep 2026
- First submitted
- 30 Mar 2022
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No