Neoadjuvant trastuzumab, pertuzumab and tucatinib without chemotherapy in HER2-positive breast cancer: the TRAIN-4 study
- Conditions
- Breast cancer
- Registration Number
- 2024-518192-61-00
- Brief Summary
To evaluate safety and feasibility of a neoadjuvant chemotherapy-free regimen with trastuzumab plus pertuzumab plus tucatinib in stage II-III HER2-positive breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 30
Signed written informed consent
Laboratory requirements within 21 days prior to enrollment: a. Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l); b. Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal). Subjects with Gilbert's syndrome may have a total bilirubin ≥2.5 × the ULN range, if no evidence of biliary obstruction exists; c. Adequate renal function: creatinine clearance >50 ml/min estimated using the Cockcroft-Gault equation or MDRD equation, or based on a 24-hour urine collection measurement
Histologically confirmed primary invasive breast cancer
Stage II – IIIA primary breast cancer according to TNM-staging (8th edition, AJCC); (largest tumor diameter DCE-MRI ≥ 2cm (cT2-3) and/or cN1-2 confirmed with FNA or histology)
HER2 overexpression defined as circumferential membrane staining that is complete, intense and in >10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy
Known estrogen- and progesterone-receptor expression of the invasive tumor a. ER-negative or PR-negative is defined as <10% of invasive tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER and/or PR
WHO performance status 0-1
Age (≥ 18 years of age)
LVEF ≥50% measured by echocardiography or MUGA
Eligible for neoadjuvant treatment
Inflammatory breast cancer, cT4 and/or cN3 tumors
Contraindications for MRI
Occult breast cancer (cT0)
Bilateral breast cancer
Current pregnancy or breastfeeding
Current or previous other malignancy unless treated without systemic therapy and more than five years ago
Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Use of a strong CYP3A4 or CYP2C8 inhibitor within five half-lives of the inhibitor, or used a strong CYP3A4 or CYP2C8 inducer within five days prior to first dose of study treatment
Known chronic liver disease
History of inflammatory bowel disease or bowel resection
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence and severity of adverse events (all grades) until 30 days after last study treatment administration Incidence and severity of adverse events (all grades) until 30 days after last study treatment administration
- Secondary Outcome Measures
Name Time Method Incidence of serious adverse events until 30 days after last study treatment administration Incidence of serious adverse events until 30 days after last study treatment administration
Incidence of progressive disease during neoadjuvant treatment -progressive disease: defined as 20% increase ΔFTV or >20% increase measured in the longest diameter on DCE-MRI or unequivocal new lesions on (18)F-FDG PET Incidence of progressive disease during neoadjuvant treatment -progressive disease: defined as 20% increase ΔFTV or >20% increase measured in the longest diameter on DCE-MRI or unequivocal new lesions on (18)F-FDG PET
Incidence of dose reductions and treatment discontinuations Incidence of dose reductions and treatment discontinuations
Radiologic complete response defined as the absence of pathologic enhancement on contrast enhanced MRI breast Radiologic complete response defined as the absence of pathologic enhancement on contrast enhanced MRI breast
Pathological complete response (ypT0/is N0) at surgery in patients treated without chemotherapy, and overall Pathological complete response (ypT0/is N0) at surgery in patients treated without chemotherapy, and overall
Residual Cancer burden (RCB, 0-III) at surgery in patients treated without chemotherapy, and overall Residual Cancer burden (RCB, 0-III) at surgery in patients treated without chemotherapy, and overall
Event-free survival (EFS) defined as the interval from registration to disease progression resulting in inoperability, recurrence, or death from any cause, whichever comes first at 3, 5 and 10 years after registration Event-free survival (EFS) defined as the interval from registration to disease progression resulting in inoperability, recurrence, or death from any cause, whichever comes first at 3, 5 and 10 years after registration
Overall survival (OS) defined as the time from registration to death from any cause at 3, 5 and 10 years after registration Overall survival (OS) defined as the time from registration to death from any cause at 3, 5 and 10 years after registration
Trial Locations
- Locations (1)
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
🇳🇱Amsterdam, Netherlands
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting🇳🇱Amsterdam, NetherlandsGabe SonkeSite contact+31205129111g.sonke@nki.nl