Trastuzumab in a Neo-adjuvant Regimen for HER2+ Breast Cancer - the TRAIN Study

Study Overview
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Brief Summary
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To determine the activity of the combination of paclitaxel, trastuzumab and carboplatin as neo-adjuvant treatment in patients with stage II or III HER2 positive breast cancer

Official Title
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Trastuzumab in a Neo-adjuvant Regimen for HER2+ Breast Cancer - the TRAIN Study

Conditions
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Breast Cancer, HER2 Positive

Intervention / Treatment
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* Drug: paclitaxel, trastuzumab and carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed infiltrating breast cancer. Stage II or stage III breast cancer.28 'Locally advanced breast cancer' patients are consequently eligible, including those with ipsilateral supraclavicular lymph node metastases. N1 status must have been demonstrated by either fine needle aspiration from an axillary lymph node or by a metastasis of >2 mm in diameter at sentinel node biopsy. Stage IIA patients are eligible if the tumor is >3 cm in diameter or if the tumor is between 2 and 3 cm in diameter but a breast conserving surgery is not possible. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy, according to one of the following definitions: >10% of invasive tumor cells showing strong complete circumferential membrane staining (score 3+) >10% of invasive tumor cells showing moderate complete circumferential membrane staining (score 2+) and demonstrating HER2 gene amplification defined as a FISH ratio of HER2 gene copies to chromosome 17 signals of >2.2. or as >5 HER2 gene copies per nucleus in CISH analysis. Patients with a negative or equivocal overall result (FISH test ratio of <2.2, <6.0 HER2 gene copies per nucleus) and staining scores of 0,1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible for participation in the trial. Age ≥18 Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Appendix B) Adequate bone marrow function (ANC >1.0 x 109/l, platelets >100 x 109/l) Adequate hepatic function (ALAT, ASAT and bilirubin <2 times upper limit of normal) Adequate renal function (creatinine clearance >60 ml/min) LVEF ≥50% measured by echocardiography or MUGA Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule Signed written informed consent Exclusion Criteria: No previous radiation therapy or chemotherapy No other malignancy except carcinoma in situ, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiation therapy. No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection. No evidence of distant metastases. Staging examinations must have included a chest radiograph, an ultrasound examination of the liver and an isotope bone scan. Abnormal uptake on the isotope bone scan can only be accepted if MRI, CT-scan, or plain radiograph excludes bone metastases. No concurrent anti-cancer treatment or another investigational drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>paclitaxel, trastuzumab and carboplatin | Drug: paclitaxel, trastuzumab and carboplatin<br>* paclitaxel; 70 mg/m2 trastuzumab; 2 mg/kg (loading dose 4 mg/kg) carboplatin; AUC = 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response (pCR) rate at surgery |  | at the completion of neo-adjuvant chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe disease-free and overall survival |  | during routine follow up visits after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, HER2 positive, neo-adjuvant, trastuzumab, paclitaxel, carboplatin