Clinical trial NCT05722795: Use of Imatinib to Convert Triple Negative Breast Cancer Into ER-positive Breast Cancer (I-CONIC)
Official title: Use of Imatinib to Convert Triple Negative Breast Cancer Into ER-positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Triple Negative Breast Cancer
Keywords: Conversion of TNBC to Luminal BC
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Sahlgrenska University Hospital
name: Lund University
First posted: 2023-02-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Window-of-opportunity trial.
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

1. Histological confirmed invasive primary triple negative breast cancer≥15 mm) with any node status.
2. Age ≥18 years

   Triple Negative subtype is defined below:
   1. Hormone receptor status: the invasive tumour shall be ER- and progesterone receptor (PR) -negative \[staining present in \<10% by immunohistochemistry (IHC)\].
   2. 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
3. No previous systemic treatment for TNBC
4. No concurrent anti-cancer treatment. Treatment with Bisphosphonates may continue.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. Normal organ function as defined below:

   1. absolute white blood cell count ≥1.5 x 109/L
   2. platelets ≥100 x 109/L
   3. haemoglobin ≥90g/dL
   4. total bilirubin ≤1.5 x institutional upper normal limit (UNL)/dL (≤ 3 x UNL for patients with Gilbert´s syndrome)
   5. ASAT, ALAT, GGT and alkaline phosphatase levels \< 1.5 × institutional UNL.
   6. albumin \>2.5mg/dL
   7. Creatinine \< 110 μmol/L
   8. T3, T4 and TSH (only patients with previous thyroid dysfunction)
7. 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.
8. Patients must be able to take (swallow) an oral medication.
9. Patients must be capable to understand and comply with the protocol and has signed the informed consent.

Exclusion Criteria:

1. Patients suitable for neoadjuvant treatment.
2. Concomitant treatment for breast cancer within 14 days before registration.
3. Unable to adhere to the study procedures.
4. 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.
5. Pregnancy and breast-feeding.
6. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ).
7. Known human immunodeficiency virus (HIV) positivity.
8. Known active Hepatitis B or Hepatitis C

Primary outcomes:
measure: To determine the proportion of patients that convert to ER expressing breast cancer
timeFrame: From surgery of the first patient to up to 100 weeks thereafter.
Secondary outcomes:
measure: Adverse events
timeFrame: From time of the first included patient to up to 100 weeks thereafter.
Other outcomes:
measure: Exploratory analyses - gene expression profiles
timeFrame: From surgery of the first patient to up to 100 weeks thereafter.
measure: Exploratory analyses - gene expression profiles
timeFrame: From time of the first included patient to up to 100 weeks thereafter.
Locations:
city: Gothenburg
country: Sweden
facility: Barbro Linderholm
Study officials:
affiliation: Sahlgrenska University Hospital
name: Barbro K Linderholm, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, Lehn S, Sjolund J, Reid S, Larsson C, Eriksson P, Anderberg C, Cortez E, Saal LH, Orsmark-Pietras C, Cordero E, Haller BK, Hakkinen J, Burvenich IJG, Lim E, Orimo A, Hoglund M, Ryden L, Moch H, Scott AM, Eriksson U, Pietras K. Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nat Med. 2018 May;24(4):463-473. doi: 10.1038/nm.4494. Epub 2018 Mar 12.
citation: Jansson S, Aaltonen K, Bendahl PO, Falck AK, Karlsson M, Pietras K, Ryden L. The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence. Breast Cancer Res Treat. 2018 Jun;169(2):231-241. doi: 10.1007/s10549-018-4664-7. Epub 2018 Jan 29.
citation: Arnedos M, Roulleaux Dugage M, Perez-Garcia J, Cortes J. Window of Opportunity trials for biomarker discovery in breast cancer. Curr Opin Oncol. 2019 Nov;31(6):486-492. doi: 10.1097/CCO.0000000000000583.