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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Imatinib 400 MG Oral Tablet
  One tablet daily 10 days before surgery.

Первичные конечные точки

• To determine the proportion of patients that convert to ER expressing breast cancer [Срок оценки: From surgery of the first patient to up to 100 weeks thereafter.]

Вторичные конечные точки (1)

• Adverse events [Срок оценки: From time of the first included patient to up to 100 weeks thereafter.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Швеция · 1 центр

• Barbro Linderholm — Gothenburg

Публикации

• 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 fact PMID 29529015
• 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. PMID 29380207
• 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. PMID 31464762

Идентификаторы

NCT: NCT05722795 · EudraCT 2020-005200-19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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