Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

Study Overview
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Brief Summary
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This study compares two schedules of upfront chemotherapy in HER positive breast cancer.

Detailed Description
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Upfront trastuzumab treatment is beneficial to patients with HER2 positive breast cancer. The potential synergistic cardiotoxicity of trastuzumab and anthracyclines has led to the development of non-anthracycline containing regimens, which have shown high pathologic complete response rates. Anthracyclines remain very active in HER2 positive breast cancer, however, and increasing evidence now supports safe combination of trastuzumab and epirubicin. Therefore, the addition of epirubicin to a non-anthracycline containing regimen may further improve outcome for patients with HER2 positive breast cancer. Several reports confirmed benefit of dual HER2 blockade by adding pertuzumab to a trastuzumab containing neoadjuvant regimen. The results of the combined treatment in the Neosphere study, however, are similar to what we found in a phase II trial using a weekly paclitaxel, trastuzumab, carboplatin combination with pCR rates of approximately 44%. Adding pertuzumab to this regimen is likely to also increase the high pCR rate and to add substantial benefit to patients.

Official Title
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Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study

Conditions
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Breast Cancer, HER2 Positive

Intervention / Treatment
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* Drug: PTC+Pertuzumab
* Drug: FEC-T+Pertuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed infiltrating breast cancer Stage II or stage III disease. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy, according to one of the following definitions: •>30% of invasive tumor cells showing strong complete circumferential membrane staining (score 3+) •HER2 gene amplification defined as >6 HER2 gene copies per nucleus by in situ hybridization. Age ≥18 Eastern Cooperative Oncology Group performance status ≤1 Adequate bone marrow function (ANC >1.5 x 109/l, platelets >100 x 109/l) Adequate hepatic function (ALAT, ASAT and bilirubin <2.5 times upper limit of normal) Adequate renal function (creatinine clearance >50 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 Absence of any medical condition that would place the patient at unusual risk. Signed written informed consent Exclusion Criteria: previous radiation therapy or chemotherapy 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. current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection evidence of distant metastases. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures. evidence of bilateral infiltrating breast cancer. Evaluation of the presence of bilateral infiltrating breast cancer may include mammography, breast ultrasound and/or MRI breast. 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FEC-T +Pertuzumab<br>Fluorouracil; 500 mg/m2; day 1 Epirubicine; 90 mg/m2; day 1 Cyclophosphamide; 500 mg/m2; day 1 Trastuzumab; 6 mg/kg (loading dose 8 mg/kg) Pertuzumab; 420 mg (loading dose 840 mg); day 1 Cycle is repeated every 21 days | Drug: FEC-T+Pertuzumab<br>* Cycle is repeated every 21 days<br>* Other names: Pertuzumab; 420 mg (loading dose 840 mg); day 1;|
| Active Comparator: PTC+Pertuzumab<br>Paclitaxel; 80 mg/m2; day 1,8 Trastuzumab; 6 mg/kg (loading dose 8 mg/kg); day 1 Carboplatin; AUC=6; day 1 Pertuzumab; 420 mg (loading dose 840 mg); day 1 Cycle repeated every 21 days | Drug: PTC+Pertuzumab<br>* Cycle repeated every 21 days<br>* Other names: Pertuzumab; 420 mg (loading dose 840 mg); day 1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with pathological complete response | To compare the efficacy of six cycles neoadjuvant PTC plus pertuzumab preceded by either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab in HER2 positive breast cancer | at week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with grade >2 adverse events as a measure of safety and tolerability | to describe the safety of the various regimens toxicity is compared between the two arms | up to week 35 | 
| identify prognostic and predictive biomarkers for pCR | To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment | within one year after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant, breast cancer, HER2 positive