Neoadjuvant treatment for HER2-positive breast cancer without chemotherapy
Neoadjuvant Trastuzumab, Pertuzumab and Tucatinib Without Chemotherapy in HER2-positive Breast Cancer: the TRAIN-4 Study
This study is testing a new treatment using tucatinib, trastuzumab, and pertuzumab for people with stage II-III HER2-positive breast cancer to see if they can be treated without chemotherapy.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | The Netherlands Cancer Institute Academic / other |
| Drugs / interventions | trastuzumab, pertuzumab, tucatinib, chemotherapy |
| Locations | 1 site (Amsterdam) |
| Trial ID | NCT06162559 on ClinicalTrials.gov |
What this trial studies
This phase 1b study evaluates the safety and feasibility of a neoadjuvant treatment regimen combining tucatinib, trastuzumab, and pertuzumab for patients with stage II-III HER2-positive breast cancer. The study aims to identify patients who can be effectively treated without chemotherapy, thereby reducing the associated toxicities. By utilizing DCE-MRI to select optimal responders, the study seeks to enhance the proportion of patients who can achieve a high pathological complete response. The focus is on assessing both the safety and efficacy of this targeted therapy approach.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with stage II-III HER2-positive breast cancer who meet specific histological and performance status criteria.
Not a fit: Patients with hormone receptor-positive tumors or those who are not eligible for neoadjuvant treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could spare patients from chemotherapy-related side effects while effectively managing their breast cancer.
How similar studies have performed: Other studies have shown promising results with HER2-targeted therapies, but this specific combination without chemotherapy is a novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Signed written informed consent
2. Histologically confirmed primary invasive breast cancer
3. Stage II - IIIA primary breast cancer according to TNM-staging (8th edition, AJCC); (largest tumor diameter on DCE-MRI ≥ 2cm (cT2-3) and/or cN1-2 confirmed with FNA or histology)
4. HER2 overexpression defined as circumferential membrane staining that is complete, intense and in \>10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy
5. 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
6. WHO performance status 0-1
7. Age ≥ 18 years
8. LVEF ≥50% measured by echocardiography or MUGA
9. Eligible for neoadjuvant treatment
10. Laboratory requirements within 21 days prior to enrollment:
1. Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l);
2. 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.
3. 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.
Exclusion Criteria:
1. Current pregnancy or breastfeeding
2. Current or previous other malignancy unless treated without systemic therapy and more than five years ago
3. Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
4. 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
5. Known chronic liver disease
6. History of inflammatory bowel disease or bowel resection
7. Contraindications for MRI
8. Inflammatory breast cancer, cT4 and/or cN3 tumors
9. Occult breast cancer (cT0)
Where this trial is running
Amsterdam
- Netherlands Cancer Institute — Amsterdam, Netherlands (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.