Ketorolac and pregabalin to modify perioperative inflammation and nerve signaling in early ER+ breast cancer

Unravelling the Local and Systemic Effects of Primary Surgery and Perioperative Use of Ketorolac and Pregabalin in Primary Breast Cancer Patients According to Adiposity

This trial will test whether giving short-term ketorolac, pregabalin, or both around surgery can blunt inflammatory and neural signals in adults having surgery for early estrogen-receptor–positive breast cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Jules Bordet Institute (other)
• Locations: 1 site (Brussels, Brussels Capital)
• Trial ID: NCT06150898 on ClinicalTrials.gov

What this trial studies

This phase II perioperative intervention gives repurposed drugs (ketorolac, pregabalin, or their combination) around the time of primary breast cancer surgery and collects blood and tumor samples before and after surgery. The goal is to measure how blocking cyclooxygenase-driven inflammation and neurotransmitter release changes tumour and systemic markers linked to recurrence, while accounting for adiposity and other confounders. Treatments include oral ketorolac and pregabalin with prospective specimen and data collection for translational analyses. The trial is conducted at a single tertiary cancer center with integrated clinical and laboratory endpoints.

Who should consider this trial

Good fit: Adult women aged 18–70 with invasive estrogen-receptor–positive (ER+) stage I–III breast cancer, tumor size ≥1.5 cm, scheduled for primary surgery and willing to provide blood and tumour samples are ideal candidates.

Not a fit: Patients with metastatic (stage IV) disease, ER-negative tumors, those not undergoing surgery, or those who cannot take NSAIDs or pregabalin (due to contraindications) are unlikely to benefit from this perioperative intervention.

Why it matters

Potential benefit: If successful, this approach could reduce surgery-driven signals that promote metastatic outgrowth and thereby lower the risk of recurrence after surgery.

How similar studies have performed: Observational data have suggested perioperative NSAIDs like ketorolac may lower recurrence risk, but combining NSAIDs with pregabalin to target neural and inflammatory pathways is novel and not yet proven in randomized trials.

Eligibility criteria

Inclusion Criteria:

Subjects must meet all of the following criteria in order to be eligible for this study:

1. Age ≥ 18 years and ≤ 70 years old
2. Female
3. Weight ≥ 35 kg
4. 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
5. Tumour size ≥ 1.5 cm, determined by diagnostic ultrasound or MRI/CT scan.
6. Stage I, II or III disease (non-metastatic)
7. In case of multifocal, multicentric unilateral or bilateral breast: Adenocarcinoma tumours are allowed provided that all foci are ER+ according to local testing
8. Subject scheduled for a primary breast cancer surgery
9. Subject is willing to provide plasma/blood and tumour samples for translational research.
10. 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
11. Subject is willing to take omeprazole and has no contraindication to omeprazole.
12. 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)
13. 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.
14. Negative serum pregnancy test for women of childbearing potential (within 30 days before start of treatment)
15. Subject is willing and able to provide written informed consent for the trial

Exclusion Criteria:

Subjects meeting one of the following criteria are not eligible for this study:

1. Subject planned for intraoperative radiotherapy
2. Subject planned for immediate reconstruction
3. Neoadjuvant BC therapy
4. Allergy to any NSAID or gabapentinoïd
5. 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)
6. Current use of the antidiabetic agent thiazolidinedione (related to interaction with pregabalin), lithium salts, probenecid, pentoxifylline or intensive diuretic therapy.
7. Current NSAID (\> twice a week the year prior to diagnosis) or pregabalin use
8. 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.
9. Active or history of peptic ulcer disease or gastro-intestinal bleeding or perforation
10. Pregnancy or lactating women
11. 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.
12. Complete or partial nasal polyposis syndrome, Quincke's oedema, bronchospasm, asthma
13. 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)
14. 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).
15. 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)
16. 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))
17. Cirrhosis or severe hepatitis.
18. 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
19. Subject with history of (severe) renal toxicity with an NSAID
20. Subject with a recent history of operations associated with a high risk of bleeding
21. 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
22. Subject with a recent history of surgery associated with a high risk of bleeding
23. 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.
24. Inadequate bone marrow function (defined as absolute neutrophil count \<1000/μL and platelet count \<100'000/μL)
25. Systemic immunosuppressive treatment (defined as systemic corticotherapy or anti-rejection treatment or interferon therapy) within the 2-years prior diagnosis
26. Psychiatric disease or antipsychotic/ antidepressant use
27. Epilepsy or any current anti-epileptic drug use
28. Obstructive sleep apnea
29. ASA≥3

Where this trial is running

Brussels, Brussels Capital

• Institut Jules Bordet — Brussels, Brussels Capital, Belgium (RECRUITING)

Study contacts

• Study coordinator: Imane Bachir, MD

Conditions: Early-stage Breast Cancer, Estrogen-receptor-positive Breast Cancer, Surgery, Inflammation, Breast cancer, Neuronal features, Ketorolac, Pregabalin