Trial to Compare the Safety, Efficacy and Immunogenicity of TX05 With Herceptin® in HER2+ Early Breast Cancer

Study Overview
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Brief Summary
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This is a Phase III, double-blind, randomized, multicenter study to compare the efficacy and to evaluate the safety and immunogenicity of TX05 (trastuzumab) with Herceptin® in subjects with HER2 positive early breast cancer.

Official Title
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A Randomized, Double-blind, Parallel Group, Phase III Trial to Compare the Efficacy, Safety, and Immunogenicity of TX05 With Herceptin® in Subjects With HER2 Positive Early Breast Cancer

Conditions
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Breast Cancer, Breast Neoplasms, HER2-positive Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer

Intervention / Treatment
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* Biological: TX05 (trastuzumab)
* Biological: Herceptin®
* Drug: Paclitaxel
* Drug: Epirubicin
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed HER 2 overexpressing invasive primary operable Stage II/IIIa breast cancer (AJCC version 7 staging criteria). Available tumor tissue for central review of HER2 status. Planned surgical resection of breast tumor. Planned neoadjuvant chemotherapy. Documentation of HER2 gene amplification or overexpression. Ipsilateral, measurable tumor longest diameter > 2 cm. Known estrogen receptor (ER) and progesterone receptor (PR) hormone status (may be performed during screening). ECOG performance status of 0 or 1. Adequate bone marrow, hepatic and renal functions. Left ventricular ejection fraction (LVEF) ≥ 50% or within institutional normal limits, measured by echocardiography or MUGA scan. Effective contraception as defined by protocol. Key Exclusion Criteria: Investigational therapy within 2 months of first dose of study drug. Bilateral breast cancer. Inflammatory breast cancer Metastases. Prior chemotherapy, biologic therapy, radiation or surgery for any active malignancy, including breast cancer. Cardiac insufficiency, myocardial infarction, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, unstable angina pectoris, uncontrolled arrhythmia or pulmonary embolus within the previous 12 months prior to 1st administration of study drug. Clinically significant active infection, poorly controlled diabetes mellitus and/or uncontrolled hypertension. Major surgery, significant traumatic injury, radiation therapy and/or grade 3 hemorrhage within 4 weeks of 1st administration of study drug. Pre-existing clinically significant Grade 2 peripheral neuropathy. Malignancy within the last 5 years (except squamous/basal cell carcinoma of the skin, cervical carcinoma in situ and superficial bladder cancer). Severe dyspnea at rest requiring oxygen therapy. Known positive HIV, acute or chronic active infection with Hepatitis B or Hepatitis C. Current pregnancy or breastfeeding. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in normal range despite optimal therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TX05 (trastuzumab)<br>• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles | Biological: TX05 (trastuzumab)<br>* 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)<br>Drug: Paclitaxel<br>* 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8)<br>* Other names: Ribotax;Drug: Epirubicin<br>* 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4)<br>Drug: Cyclophosphamide<br>* 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)<br>|
| Active Comparator: Herceptin®<br>• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles | Biological: Herceptin®<br>* 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)<br>Drug: Paclitaxel<br>* 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8)<br>* Other names: Ribotax;Drug: Epirubicin<br>* 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4)<br>Drug: Cyclophosphamide<br>* 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) | Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0). | 3-7 weeks following last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR. | End of Treatment (Week 24) or Early Termination Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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trastuzumab, Herceptin