Clinical trial NCT06710197: IL-1 Inhibition in Early TNBC
Official title: IL-1 Inhibition for Patients With Early Stage Triple Negative and ER-low Breast Cancer: a Window-of-opportunity Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Early Stage Triple Negative ER Low Breast Cancer
Keywords: WOO
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2024-11-29
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will examine changes in the tumor microenvironment (TME) induced by 14 days of pre-operative IL-1-inhibiting therapy among patients with early breast cancer (including TNBC and ER-low positive \[1-9%\]). Key immune biomarkers (TILs, TAMs, NK cells, IL-1β and inflammasome component expression) will be evaluated at baseline and following 14 days of IL-1 antagonist therapy (Anakinra) using paired tissue specimens. A total of 50 patients will be recruited across 2-5 institutions, randomized 4:1 to treatment (n=40) versus control (n=10).
Primary purpose: BASIC_SCIENCE

Brief summary: This study will examine changes in the tumor microenvironment (TME) induced by 14 days of pre-operative IL-1-inhibiting therapy among patients with early breast cancer (including TNBC and ER-low positive). Key immune biomarkers (TILs, TAMs, NK cells, IL1\[beta\] and inflammasome component expression) will be evaluated at baseline and following 14 days of IL-1 antagonist therapy (Anakinra) using paired tissue specimens.


Eligibility criteria: Inclusion Criteria:

* For inclusion in this study, patients must fulfill all the following criteria:

  1. Age \> 18 years
  2. Histologically confirmed non-metastatic invasive adenocarcinoma of the breast meeting one of the following criteria:

     i. Clinical stage T1a/b N0 TNBC ii. Clinical stage T1a/b N0 ER-low (1-9%)
  3. Not planned for neoadjuvant chemotherapy

Exclusion Criteria:

Patients who satisfy any of the following exclusion criteria are NOT eligible for this study.

1. Male Gender
2. HER2 positive breast cancer
3. Second primary cancer
4. Multifocal early breast cancer
5. Pre-existing inflammatory arthritis
6. Pregnancy or lactating.
7. Platelets ≤ 100x109/L. ANC ≤ 1.5 x109/L. Hemoglobin ≤ 80 g/L
8. ECOG≥2
9. Clinically significant bacterial, fungal, parasitic or viral infection, which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
10. Known active hepatitis A, B, C or who are HIV-positive or who are at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (i.e., hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
11. Primary immunodeficiency such as X-linked agammaglobulinemia or common variable immunodeficiency.
12. Active and inactive ('latent') tuberculosis infection or suspicion of active tuberculosis. If no suspicion of active tuberculosis, testing is not required.
13. Use of glucocorticoids above the equivalent of 10 mg of prednisone daily within 4 weeks prior to treatment with Anakinra.
14. Major surgery within 4 weeks prior to treatment.
15. History of malignancy in the past 3 years except for treated, early-stage squamous or basal cell carcinoma of the skin or carcinoma-in-situ of the cervix.
16. History or current diagnosis of uncontrolled or significant cardiac disease, including any of the following: a. myocardial infarction within last 6 months. b. uncontrolled congestive heart failure. c. unstable angina within last 6 months. d. exertional angina. e. clinically significant (symptomatic) cardiac arrhythmias (e.g., bradyarrhythmia, sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
17. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
18. Presence of moderate or severe renal function impairment (estimated creatinine clearance \<60 mL/min/1.73m2).
19. Patients with mild, moderate, or severe hepatic impairment or inadequate liver function defined by any of direct bilirubin, alanine amino transferase (ALT), or aspartate aminotransferase (AST)\>2.5 x upper limit of normal (ULN). Patients with Child-Pugh score \>5 are also excluded.
20. Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening or 5 half-lives (whichever is longer) prior to the first dose of investigational product.
21. Significant concurrent, uncontrolled medical condition which, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.
22. Known hypersensitivity to E-coli derived proteins, Anakinra or any component of the product.

Primary outcomes:
measure: To determine the changes in the breast cancer TME in paired patient samples (core biopsy and surgical specimen) before and after 14 days of treatment with the IL-1 receptor antagonist, Anakinra.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
References: