ER-positive/HER2-negative invasive lobular carcinoma MedDRA version: 20.0 Level: PT Classification code 10073096 Term: Invasive lobular breast carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Rozlytrek
Product Name: entrectinib
Pharmaceutical Form: Capsule
INN or Proposed INN: ENTRECTINIB
Current Sponsor code: Entrectinib IJB 200mg
Concentration unit: mg milligram(s)
Concentrat
Sponsors
Institut Jules Bordet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female 2. Age = 18 years 3. Histological diagnosis of invasive lobular breast adenocarcinoma that is ER+, and HER2- as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing. 4. Multifocal unilateral or bilateral breast adenocarcinoma tumours are allowed if all tested foci are lobular, ER+ and HER2-. o ER positive (ER+ is defined as having an IHC of 1% or more and/or an Allred of 3 or more and HER2-). o HER2 negative (HER2- is defined as having an IHC of 0 or 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number =65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: Subjects who exhibit any of the following conditions at screening will not be eligible for admission into the study. 1. Clinical T4 disease including inflammatory breast cancer and/or cN2 or cN3. 2. Prior history of invasive cancer in the past 5 years except basal or squamous cell carcinoma of skin that has been definitively treated. 3. Known hypersensitivity to the study drugs or excipients. 4. Hyperuricemia > Grade 1 5. Any illness or medical condition that is unstable or could jeopardize the safety of the subject or her compliance with study requirements. 6. Subjects unable to swallow oral medications. 7. Prior intake of letrozole, any ROS1 inhibitor, any TRK inhibitor or anticancer therapy (including endocrine therapy). 8. Concurrent treatment with strong or moderate CYP3A inhibitor. 9. Concurrent treatment with any of the drugs not permitted, i.e. strong CYP3A inducers and drugs known to cause QTc interval prolongation. 10. Significant cardiac disease, including recent (less than 6 months) myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias. 11. LVEF = 55% measured by ECHO or MUGA (ECHO should be the preferred method) 12. QTc exceeding 450 msec, history of prolonged QTc interval prolongation; risk factors for torsade de pointes; other concomitant medications that may prolong QTc; family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP); uncorrected electrolyte imbalances 13. Pregnant or lactating women. 14. Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis 15. Peripheral neuropathy = Grade 2 16. Active gastrointestinal disease (e.g., Crohn’s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of endocrine therapy + entrectinib in women with ER-positive/HER2-negative early breast cancer of the lobular subtype;Secondary Objective: To further evaluate the efficacy of the combination by pathology. To further evaluate the efficacy of the combination by imaging. To evaluate the safety of endocrine therapy + entrectinib. ;Primary end point(s): RCB 0/1 by local evaluation in all enrolled subjects. ;Timepoint(s) of evaluation of this end point: end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pathologic complete response (pCR) rate in breast and axilla (ypT0/Tis ypN0) by local evaluation. Tumour objective response assessed by locally-assessed breast MRI via modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1.). Incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v5.0). ;Timepoint(s) of evaluation of this end point: end of the trial | — |
Countries
Belgium, France
Contacts
Public ContactCTSU
Institut Jules Bordet
Outcome results
None listed