Use of Imatinib to Convert Triple Negative Breast Cancer Into ER-positive Breast Cancer (I-CONIC)

Study Overview
=================
Brief Summary
-----------------
This is a single centre Window-of-Opportunity trial investigating the efficacy and feasibility of short term imatinib in patients with newly diagnosed triple negative breast cancer (TNBC) planned for surgery, with tumours ≥ 15 mm, any status in the axilla when neoadjuvant treatment not is considered as an option. The primary aim is to determine the proportion of patients that converts to estrogen receptor (ER) positive breast cancer in the removed breast cancer tissue at surgery.

Detailed Description
-----------------
This is a single centre Window-of-Opportunity trial that will investigate the efficacy and feasibility of short term (10 days) imatinib in patients with newly diagnosed TNBC planned for surgery, with tumours ≥ 15 mm, any status in the axilla and when neoadjuvant treatment not is considered as an option. Imatinib is given at a dose of 400 mg daily. The primary aim is to determine the proportion of patients that converts to ER positive breast cancer in the removed breast cancer tissue at surgery. The secondary aim is to evaluate the safety and adverse events (AE) will be collected throughout the study, from informed consent until 30 days after the last dose of the IMP imatinib. AEs will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Official Title
-----------------
Use of Imatinib to Convert Triple Negative Breast Cancer Into ER-positive Breast Cancer

Conditions
-----------------
Breast Cancer, Triple Negative Breast Cancer

Intervention / Treatment
-----------------
* Drug: Imatinib 400 MG Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histological confirmed invasive primary triple negative breast cancer≥15 mm) with any node status. Age ≥18 years Triple Negative subtype is defined below: Hormone receptor status: the invasive tumour shall be ER- and progesterone receptor (PR) -negative [staining present in <10% by immunohistochemistry (IHC)]. HER2 status: the invasive tumour shall be Human Epidermal growth factor Receptor (HER) 2-negative by the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines No previous systemic treatment for TNBC No concurrent anti-cancer treatment. Treatment with Bisphosphonates may continue. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Normal organ function as defined below: absolute white blood cell count ≥1.5 x 109/L platelets ≥100 x 109/L haemoglobin ≥90g/dL total bilirubin ≤1.5 x institutional upper normal limit (UNL)/dL (≤ 3 x UNL for patients with Gilbert´s syndrome) ASAT, ALAT, GGT and alkaline phosphatase levels < 1.5 × institutional UNL. albumin >2.5mg/dL Creatinine < 110 μmol/L T3, T4 and TSH (only patients with previous thyroid dysfunction) Patients of childbearing potential must have a negative serum or urine pregnancy test within 8 days prior to start of imatinib treatment.. Female patients of childbearing potential must agree to usecontraceptive methods with a failure rate below 1% per year during the study treatment and at least 90 days after the last dose of imatinib. Patients must be able to take (swallow) an oral medication. Patients must be capable to understand and comply with the protocol and has signed the informed consent. Exclusion Criteria: Patients suitable for neoadjuvant treatment. Concomitant treatment for breast cancer within 14 days before registration. Unable to adhere to the study procedures. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, neurological conditions, physical examination or laboratory findings) that may interfere with the planned treatment or affect patient compliance. Pregnancy and breast-feeding. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ). Known human immunodeficiency virus (HIV) positivity. Known active Hepatitis B or Hepatitis C

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Window-of-opportunity trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short term Imatinib<br>Imatinib 400 mg x 1 for 10 days before surgery. | Drug: Imatinib 400 MG Oral Tablet<br>* One tablet daily 10 days before surgery.<br>* Other names: No other intervention;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the proportion of patients that convert to ER expressing breast cancer | ER expression is determined by immunohistochemistry | From surgery of the first patient to up to 100 weeks thereafter. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | AEs are registered according to National Cancer Institute (NCI) CTCAE version 5.0. | From time of the first included patient to up to 100 weeks thereafter. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Conversion of TNBC to Luminal BC