Using imatinib to convert triple-negative breast cancer into ER-positive breast cancer

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

This gives 10 days of imatinib to people with newly diagnosed triple-negative breast cancer before surgery to see if their tumors become estrogen receptor (ER)–positive.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vastra Gotaland Region (Government)
• Drugs / interventions: imatinib
• Locations: 1 site (Gothenburg)
• Trial ID: NCT05722795 on ClinicalTrials.gov

What this trial studies

This single-center window-of-opportunity trial will test short-term imatinib given for 10 days before surgery in adults with newly diagnosed triple-negative breast cancer and tumors at least 15 mm. Participants take imatinib 400 mg orally once daily and then proceed to planned surgical removal of the tumor. The primary outcome is the proportion of tumors that convert from ER-negative to ER-positive on the surgical specimen, and adverse events are collected through 30 days after the last dose using CTCAE v5.0. Patients who have received prior systemic therapy or who require neoadjuvant treatment are not eligible.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed invasive triple-negative breast cancer measuring ≥15 mm who are planned for upfront surgery, have not received prior systemic therapy, and have ECOG performance status 0–1.

Not a fit: Patients with tumors smaller than 15 mm, prior systemic treatment, poor organ function, or those already planned for neoadjuvant therapy are unlikely to gain benefit from this short preoperative treatment.

Why it matters

Potential benefit: If successful, some patients with TNBC could become eligible for hormone therapies, potentially broadening treatment options.

How similar studies have performed: This is a novel clinical application of imatinib—while imatinib is effective in other cancers, few prior clinical studies have shown conversion of TNBC to ER-positive status.

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

Where this trial is running

Gothenburg

• Barbro Linderholm — Gothenburg, Sweden (Recruiting)

Study contacts

• Principal investigator: Barbro K Linderholm, MD, PhD — Sahlgrenska University Hospital
• Study coordinator: Barbro K Linderholm, MD, PhD

Conditions Breast Cancer; Triple Negative Breast Cancer; Conversion of TNBC to Luminal BC